key: cord-273019-hbpfz8rt
authors: Glingston, R. Sahaya; Deb, Rachayeeta; Kumar, Sachin; Nagotu, Shirisha
title: Organelle dynamics and viral infections: at cross roads
date: 2018-06-25
journal: Microbes Infect
DOI: 10.1016/j.micinf.2018.06.002
sha: 
doc_id: 273019
cord_uid: hbpfz8rt

Viruses are obligate intracellular parasites of the host cells. A commonly accepted view is the requirement of internal membranous structures for various aspects of viral life cycle. Organelles enable favourable intracellular environment for several viruses. However, studies reporting organelle dynamics upon viral infections are scant. In this review, we aim to summarize and highlight modulations caused to various organelles upon viral infection or expression of its proteins.

A unique feature of eukaryotic cells is the presence of distinct membrane bound structures called organelles. This subcompartmentalization of eukaryotic cells is very essential for its optimum function. Organelles achieve this due to the presence of a unique set of proteins and distinctive lipid composition that determines their function. They are dynamic and interact with the surrounding organelles to regulate their biogenesis and function [1, 2] . Association of organelle dysfunction with human diseases/ disorders is reported and widely acknowledged [3] . It is interesting that not only organelles are required for proper functioning of cells, but are also required for the successful infection of a virus [4, 5] . It is well established that viruses develop alternate strategies to survive in the cells. The steps of the viral life cycle include entry, translation, replication, assembly and egress [6] . Moreover, viruses have developed remarkable ways to complete their life cycle by targeting specific cell organelles and processes. Organelles like mitochondria, ER, peroxisomes play an important role in innate immunity and host defence [7] . Recently lipid droplets have also been reported to be essential for innate response against viral infection [8] .

The viral life cycle is also a dynamic process that leads to the extensive host cellular reorganization. Characterization of this spatiotemporal reorganization is a key step in order to understand the molecular mechanism of viral infection. Localization of the viral proteins to an appropriate sub-cellular compartment is part of the strategy to hijack the host machinery and necessary pathways leading to establishment of an infection [9, 10] . With the advent of several modern microscopy and proteomics methods, it is now clear that the localization and function of many host proteins are altered due to viral infections. Not only the host proteins but the intracellular localization of the viral proteins and their interactions with the host proteins are also extensively studied using these methods [10] . However, currently our understanding of organelle dynamics during viral infections is still at its infancy. Current review briefly summarizes our knowledge of the various cell organelles/compartments following virus infection. This topic at the interjection of virology and cell biology represents an emerging research area of molecular investigations in virology.

Presence of nucleus that houses the genome is what distinguishes eukaryotic cells from prokaryotes (Fig. 1 ). It is a double membrane organelle and is the site for gene regulation and transcription. Nuclear envelope comprising of nuclear pores is the barrier between the nuclear content and the rest of the cell. Nucleolus is the region where ribosomal subunit assembly takes place in the nucleus. Sub nuclear structures comprising of several proteins which regulate many cellular processes like apoptosis, DNA damage, etc are called PML-NBs.

Many DNA and RNA viruses depend on the host nuclear proteins for their replication [11] . Several strategies are used by viruses in order to deliver its genome to the host cells [12] . Usually, when cells undergo mitosis, there is a temporary disassembly of the nuclear envelope (NE) which allows some viruses to enter into the nucleus [13] . Entry and integration of murine leukemia virus (MLV) into host nucleus depends on the NE breakdown during mitosis [14] . Various human immunodeficiency virus (HIV) preintegration complex proteins, such as the matrix [15] , Vpr [16] , integrase [17, 18] were found to contain nuclear localization signal (NLS) in their genome sequence. This NLS interacts with the nuclear transport receptors, which transports the viral proteins through the nuclear pore complex (NPC). Similarly, the influenza virus nucleoprotein (NP) present in the viral ribonucleoprotein complex (vRNP) contains NLS1, NLS2 and NLS3, which helps in its binding to cellular importins resulting in transportation of the vRNP to the nucleus [19e21] .

In another strategy, the capsid of certain viruses gets attached to the cytoplasmic side of the host NPC either directly or with the help of importins. This interaction acts as a signal for capsid disassembly followed by entry of the viral genome along with their proteins through the NPC into the nucleus [12] . Studies on the herpes simplex virus-1 (HSV-1) infection on Vero, BHK-21 and PtK 2 cells reported transportation of viral tegument-capsid by dynein to the cytoplasmic side of NPC [22, 23] . The HSV-1 capsid binds to NPC with the help of importin b and subsequently releases DNA into the nucleus through the NPC [24] . Similarly, the capsid protein of adenovirus (Ad) on binding with the nuclear transport protein Nup214 attaches to the cytoplasmic side of NPC and releases the genetic material into the nucleus [25] . Some small viruses such as hepatitis B virus (HBV), baculovirus, etc were found to cross the NPC and release their genome at the nuclear side of NPC or within the nucleus [12] . The capsid protein of HBV was reported to interact with NPC via the nuclear receptor Nup153 in Xenopus laevis oocytes [26] . Furthermore, this binding depends on importin a, b and phosphorylated core protein present on its capsid [27] . Upon infection, HBV capsid enters the nucleus through the NPC and subsequently releases its genome into the nucleoplasm [28] .

Similarly, capsid proteins of simian virus 40 (SV40) were found to enter the nucleus through NPC [29] . It has been reported that the disruption of the NE and nuclear lamina temporarily aid the nuclear entry of viruses such as parvoviruses [30] . Disruption of NE in Xenopus oocytes and both NE and nuclear lamina in mouse fibroblast cells upon parvovirus infection and minute virus of mice (MVM) was reported using electron microscopy analysis [30, 31] . Presumably, viruses evolved different mechanisms to enter nucleus in order to facilitate their replication cycle and survivability inside the host cells.

After the successful entry into the nucleus, both DNA and RNA viruses exploit various nuclear components such as nucleolus, promyelocytic leukaemia nuclear body (PLN) and/or nuclear proteins in order to facilitate their replication (Fig. 2) [11] . Nucleolin, fibrillarin and B23 (nucleophosmin) are examples of nucleolar proteins reported essential for various functions like post transcriptional process, ribosome assembly, etc [32] . These multifunctional host nucleolar proteins were reported to be incorporated into the replication and translation complex of many viruses [11] . Many DNA viruses like HSV and Ad were reported to be involved in relocalization or disruption of the host nucleolar proteins [11] . For instance, the transfection of the recombinant UL24 protein of HSV-1, tagged with an N-terminal hemagglutinin in Vero cells resulted in the redistribution of nucleolin and B23 [33, 34] . Another nucleolar protein fibrillarin was also found to be redistributed in spots throughout the nucleus but in an UL24 independent manner [33] . The core protein of Ad was found to be associated with the nucleolus in HeLa cells [35] . Further studies showed that this association results in the relocation of the nucleolin to the cytoplasm of the infected cells [36] . The Ad-induced relocation of nucleolin was proposed to be a strategy used by virus to suppress its activity [36] . Additionally, infection of HeLa cells with Ad resulted in inhibition of synthesis and maturation of rRNA [37] .

Nucleolar localization of the viral capsid and RNA binding proteins of many RNA viruses has been reported [11] . For example, the encephalomyocarditis viral (EMCV) proteins 2A and 3BCD and human rhinovirus HRV 3C protease were found to localize to the nucleoli resulting in inhibition of cellular RNA transcription [38, 39] . It has been reported that the expression of Tat and Rev proteins of HIV-1 in COS7 cells resulted in their accumulation in dense fibrillar component in the nucleolus [40] . Moreover, Rev protein was reported to be involved in deforming the nucleolar architecture [40] . Similarly, the viral N protein was found to be localized to the nucleolus in addition to the cytoplasm upon infection of coronavirus resulting in delayed cell cycle to facilitate viral assembly [41] . Poliovirus (PV) or rhinoviruses interact with nucleolin and blocks the nuclear import leading to accumulation of nucleolin in the cytoplasm of the infected cells [42] . The accumulated nucleolin interacts with the internal ribosome entry site (IRES) element present in the upstream 5 0 end of the viral genome to stimulate its translation [43] . On the other hand, these changes result in the shutdown of cellular transcription leading to the downregulation of the host defence mechanism [42] . Infection of human respiratory syncytial virus (HRSV) in A549 cells resulted in depletion of nucleolin [44] . Although, both DNA and RNA viruses behave differently towards acquiring the nuclear niche however the goal being to establish control over cellular transcription and favour its genome over the host. 

PML NB is another subnucleolar component, which contains proteins such as PML and Sp100. These proteins are induced by interferons and hence PML NB can act as a target for viruses to escape the antiviral signalling response [45] . Redistribution of the PML NB has been reported upon infection of HSV-1 to BHK-21 cells [46] . Similarly, EBNA LP protein of Epstein-Barr virus (EBV) was found to displace Sp100 from PML NBs in Burkitt's lymphoma and Hep2 cells [47] . The viral E4-ORF3 protein induced reorganization of PML NBs into elongated track like structures upon infection of CV1 cells with human Ad5 [48] . Later, it was found that this reorganization was responsible for the downregulation of the host antiviral response [49] . Another example is the infection of human foreskin fibroblasts (HFFs) with human cytomegalovirus (HCMV) resulting in the accumulation of pp71 at PML NBs in the infected cells [50] . Further studies showed that pp71 was responsible for the proteasomal degradation of PML-NB protein Daxx, which is important for inducing intrinsic immune response against HCMV infection [50] . Some RNA viruses also result in the redistribution and degradation of host PML NBs in order to neutralize the antiviral response. The RING finger protein Z of lymphocytic choriomeningitis virus interacts with PML protein and leads to the redistribution of PML-NBs from the nucleolus to the cytoplasm [51] . The expression of 3C protease of EMCV in CHO cells was reported to target PML-NBs and promote its degradation in proteasome and by SUMO-dependent mechanism [52] . Interestingly, CHO cells infected with rabies virus were reported to contain enlarged PML NBs [53] .

Disruption of the nucleocytoplasmic trafficking in the host cells is another major alteration caused due to viral infections ( Fig. 2 ) [54] . Two conserved proteins pUL50 and pUL53 of HCMV were reported to remodel the nuclear lamina of HELFs (primary human lung fibroblasts) for the budding of virions [55] . Interaction between human papillomavirus (HPV) and host mitotic chromosomes has been documented [56] . Infection of porcine bone marrow cells with African swine fever virus (AFSV) resulted in fragmentation of the nucleus [57] .

The organelle found in continuation with the nucleus in a cell is the ER (Fig. 1) . Protein synthesis and folding (rough ER), lipid synthesis, calcium regulation (smooth ER), etc are some of the important functions of the ER. Multiple structural domains of the ER are reported which enable it to serve as a site for various important functions in a cell.

Several morphological alterations of ER such as vesicle formation, invagination of the membrane, zippered appearance, etc have been reported upon viral infection in different cell lines (Fig. 2) . The large malleable surface of the ER aids viruses to form protective compartments to set up their replication machinery. These compartments known as viroplasm not only concentrate viral and host proteins required for viral genome replication but also protect the viral genome from cellular nucleases [58] . In order to construct these compartments, viruses alter host's fatty acid metabolism, induce rearrangement of the membrane constituents and also recruit cellular machinery to produce proteins essential for its replication [59, 60] . Infection of vaccinia virus (VACV) in BS-C-1, HeLa and RK-13 cells leads to the formation of VACV membranes derived from the ER membrane [61] . In case of dengue virus (DENV-2), the genomic RNA was observed to localize over the rough ER in C6/36 Aedes albopictus cells [62] . DENV infection in Human hepatoma 7 (Huh7) cells leads to invagination of ER membrane resulting in the formation of spherules or vesicles containing double stranded RNA [63] . HeLa cells and COS-1 cells on infection with PV 1 cause formation of single membrane tubules which later mature into double membrane vesicles (DMVs) [64, 65] . Similarly, severe acute respiratory syndrome corona virus (SARS-CoV) induced formation of ER derived DMVs upon infection of Vero cells [66, 67] . Zippered appearance of ER was observed upon infection of infectious bronchitis virus (IBV) on mammalian, avian and tracheal epithelial cells [68] . Studies with the plant viruses like the potato virus X (PVX) reported TGBp2 protein induced reorganization of the ER and appearance of vesicular structures in tobacco plants [69] . Effect of the viral protein expression on sterol biosynthesis apart from the alterations in ER morphology have also been reported [59, 70] .

Several viral proteins need to be glycosylated at their N-terminal to ensure proper folding and for the incorporation into virions [71] . Hence, a common phenomenon observed upon viral infection is interference with the host post translational machinery and competition with the cellular proteins to undergo these modifications [72] . For example, protein pORF2 of hepatitis E virus (HEV) gets glycosylated in the ER upon its expression in COS-1 cells and Huh7 mammalian cells [73, 74] . This increased biosynthetic load is proposed to increase in accumulation of malformed proteins resulting in ER stress (Fig. 2) . ER gets relieved from this stress by inducing a pathway called unfolded protein response (UPR) pathway [72] . UPR serves to enhance the cell's degradation ability in order to establish ER homeostasis [72] . Transport of misfolded, misassembled proteins from the ER to the cytosol and clearance by the ubiquitin proteasome system takes place via the ER associated degradation (ERAD) pathway [72] . However, some viruses use ERAD pathway for their advantage by co-opting ERAD to disassemble and gain access to the cytosol of the host cell [75] . Upon SV40 infection of CV-1, HeLa and 3T6 cells, induction of ERAD factors in turn induce ER membrane reorganization into distinct subdomains called foci and the accumulation of SV40 in these foci was observed [76] . Later, SV40 particles travel across the ER membrane to reach the cytosol [76] . Many enveloped and non-enveloped viruses that exploit ER functions like UPR, ERAD to facilitate their replication have been discussed elsewhere [71] .

In addition to the above listed mechanisms, ER mediated Nlinked glycosylation plays a very important role in the survival of the viruses. It has been very elegantly demonstrated that the biogenesis of influenza could modulate the host immune response [77] . Similarly, the role of N-glycans in the host immunity against HIV has been documented [77] . These studies corroborate to a common point where the level of glycosylation in the viral surface glycoproteins could alter their antigenicity.

Mitochondria are double membrane bound organelles that comprise their own genome ( Fig. 1 ). They are involved in various functions like fatty acid metabolism, apoptosis, calcium homeostasis, etc. Considered evolutionarily the oldest organelle of a eukaryotic cell, they are indispensable as power house of the cell.

Mitochondrial morphology is maintained by a series of interlinked events namely mitochondrial fusion, fission and mitophagy [78] . Mitochondrial fusion helps in exchanging matrix metabolites and intact mitochondrial DNA while mitochondrial fission helps in sorting impaired mitochondria from the healthy population which are further eliminated by a process called mitophagy [79] . All the above dynamic events are altered upon viral infection in order to facilitate its replication (Fig. 2) [80] . For example, it was reported that HBV infection in the cell induces mitochondrial fission followed by mitophagy in order to attenuate apoptosis [81] . On the other hand, expression of ORF-9B protein of SARS-CoV virus promoted mitochondrial fusion in HEK293 cells [82] .

Upregulation of mitophagy and degradation of the mitochondrial antiviral signalling protein (MAVS) in order to attenuate the antiviral immune response in non-small cell lung cancer (NSCLC) cells was reported upon measles virus infection [83] . The expression of matrix protein (M) of human parainfluenza virus type 3 (HPIV3) in HEK293T and HeLa cells was reported to induce mitophagy resulting in the suppression of type1 interferon response [84] . HBV induces mitophagosome formation which upon fusion with lysosomes leads to mitophagy and prevents apoptosis, thus facilitating persistent infection in the Huh7 cells [81] . Similarly, Newcastle disease virus (NDV) was reported to induce mitophagy, which promotes NDV replication by preventing caspase dependent apoptosis in human non-small cell lung cancer A549 cells [85] . Viruses can alter the intracellular distribution of mitochondria either to prevent the release of mediators of apoptosis or to meet their energy requirement during replication by concentrating them near their viral factories [86] . HBV X protein induces the perinuclear clustering of mitochondria in Huh7 cells [87] and AFSV leads to the transport of mitochondria to viral assembly sites in Vero cells [88] .

Mitochondrial DNA codes for proteins essential for respiratory functions of a cell. Certain viruses evade the mitochondria associated antiviral response by damaging the host cell mitochondrial DNA, which is essential for synthesizing enzymes for optimum mitochondrial function [86] . For example, mitochondrial DNA degradation is induced in mammalian cells upon expression of UL12.5, an amino-terminally truncated UL12 isoform of HSV-1 [89] . Raji cell lines infected with hepatitis C virus (HCV) also exhibit mitochondrial DNA depletion [90] .

Maintenance of mitochondrial/cellular Ca 2þ homeostasis is vital for various cellular functions. Many viruses are involved in altering the mitochondrial calcium homeostasis in order to meet their needs during replication [86] . HCMV upon infection causes calcium influx into mitochondria from ER [91] . On the other hand, expression of 2B protein of coxsackievirus resulted in reduced signalling of Ca 2þ between the ER-Golgi and the mitochondria in HeLa cells resulting in suppression of apoptosis [92] . Rotavirus was also reported to alter the calcium homeostasis in the host cell throughout its life cycle [93] .

Mitochondria are the major source of ROS in a cell and a balance between ROS production and scavenging is crucial for optimum functioning of the cells. Upon viral infection mitochondria undergo oxidative stress and result in an increased production of ROS which in turn reduces virus replication [86] . Interestingly, ROS is also involved in activating many host cellular pathways favourable for viral replication and pathogenesis. Several viruses like HIV, HCV, AdV, EBV, etc result in increased oxidative stress upon infection [86] . On the other hand, both increase and decrease of oxidative stress is employed as a survival strategy by HBV [94, 95] .

Many viral proteins reach mitochondria through the mitochondria-associated membrane [96] a sub-compartment of the ER or are targeted directly from the cytosol and result in an altered mitochondrial permeability transition pore (MPTP) [97] . MPTP is also responsible for the maintenance of MMP and provides energy for ATP synthesis. Altering MPTP leads to passive swelling, outer membrane rupture, osmotic water flux, and release of proapoptotic factors leading to cell death [98] . In general, increased MMP induces apoptosis, while decreased MMP prevents apoptosis [86] . Viruses are proposed to decrease MMP to prevent cell death in order to promote their replication. However, in later stages, they may trigger an increase in MMP to release the progeny virions by apoptosis [86] . The M11L protein of myxoma pox virus prevents the loss of MMP in Cos-7 monkey kidney cells, HeLa cells, THP-1 human monocytes and Jurkat T lymphocytes [99] . On the other side, the R protein of HIV-1 induces the loss of MMP in CEM-C7 and Jurkat cells and results in apoptosis [100] .

Viruses alter the host mitochondrial metabolic pathways in order to maintain cellular energy homeostasis essential to ensure efficient replication and to avoid mitochondrial antiviral response particularly in case of slow replicating virus [101] . Some viruses modulate the normal cells to increase aerobic glycolysis and use glucose biosynthetically, which helps especially enveloped viruses to increase their available pool of fatty acids, lipids and nucleotides during their replication [102, 103] The feline leukemia virus infection on lung fibroblasts (FLF-3) resulted in a 30e40% increase in glucose uptake and lactic acid production [104] . An increase in the lactic acid production upon infection of the chick embryo cells with Rous sarcoma virus was reported [105] . HCMV upon infection of HFFs, human retinal pigment epithelial cells (ARPE19), human embryonic lung fibroblasts (MRC5) and Vero cells enhances glycolytic flux and directs the supply of carbon from glucose to TCA cycle. This helps to facilitate fatty acid biosynthesis while HSV-1 upon infection of same cell lines directs the central carbon metabolism in order to induce the production of pyrimidine nucleotide components [106] . HCV core protein suppresses mitochondrial complex 1 activity and impaired function of electron transport cycle leading to ROS accumulation in hepatoma cells of transgenic mice [107] .

Mitochondrial involvement in virus survival is quite relevant to the fact that viruses require a source of energy to favour the active processes involved in their life cycle.

Peroxisomes are single membrane bound dynamic organelles required for b-oxidation of fatty acids and ROS metabolism (Fig. 1) .

They have developed diverse functions which are organism and environment dependent. They are unique with respect to proliferation, as they can increase in number by both growth and division of pre-existing organelles and formation of new organelles from the ER.

Many viruses or viral proteins are reported to localize to peroxisomes and/or exploit their functions to facilitate their replication in the host cells [108] . Presence of a peroxisome targeting signal (PTS) in the protein sequence is reported to be essential for targeting proteins into the peroxisomes [109] . However, it was also proposed that viral proteins without PTS may get associated with host peroxisomal proteins in the cytosol which then ferry the viral protein into the peroxisomes in a piggyback fashion [108] . For instance, HCMV encodes a protein called vMIA reported to be localized to peroxisomes in HFFs and HepG2 cells [110] . The vMIA interaction with the host Pex19 protein aids the viral protein localization to the peroxisomes. Fragmentation of peroxisomes upon vMIA expression in HepG2 was also reported [110] . In addition, peroxisomal localization of two cymbidium ring spot viral proteins p33 and p92 was reported in yeast [111] . A role for peroxisomes in the replication of TBSV has also been reported. The viral replication protein p33 interacts with the host peroxisomal protein Pex19 for its targeting to the peroxisomal membrane and subsequent replication [112, 113] . The host hsp70 protein was reported to promote the localization of the viral replication proteins to the peroxisomes in yeast cells [114] . N-terminal protease N pro of pestivirus is another example of a viral protein that is associated with peroxisomes and facilitates its survival and replication [115] .

Some members of the family tombusviridae are involved in remodelling the peroxisomal membrane resulting in the formation of vesicular structures called "profoundly modified peroxisomes" or "peroxisome derived multivesicular bodies" [108] . For example, the infection of cymbidium ring spot virus resulted in the formation of small vesicles at the periphery of the peroxisomes in plant leaf tissues [116] . At the later stage of infection, the entire peroxisomal matrix is occupied by these vesicles [116] . Similarly, the cucumber necrosis virus (CNV) induces the formation of peroxisomal vesicles in which the viral RNA replication occurs in yeast cells [117] . Studies revealed upregulation of peroxisomal biogenesis in endothelial cells upon latent infection of Kaposi's sarcoma associated herpes virus [118] . It was also reported that proteins involved in peroxisomal lipid metabolism were essential for the survival of latently infected human dermal microvascular endothelial cells and lymphatic endothelial cells [118] . Interestingly, HIV infection reduces the number of peroxisomes in infected cells due to upregulation in the levels of microRNAs that inhibit production of peroxisome biogenesis factors [119] .

It has been reported that the West Nile virus (WNV) and DENV infection on A549 and HEK293T cells result in the degradation of peroxisomes [120] . The capsid proteins of both DENV and WNV were reported to interact with the peroxisomal protein Pex19 required for peroxisome biogenesis. Degradation and redistribution of Pex19 from perinuclear region to juxtanuclear region was reported in the infected cells. In addition, reduced level of the antioxidant enzyme catalase was observed in the infected cells. These alterations resulted in an impairment of early antiviral signalling of the peroxisomes.

Expression of the PTS containing VP4 protein of the rotavirus, in MA104 cell lines resulted in peroxisomal localization [121] . The role for such a localization was speculated to utilize the peroxisomal lipid metabolism for the supply of cholesterol for lipid raft synthesis, required for the viral replication. Peroxisomal b-oxidation metabolism leads to the production of myristoyl-CoA by shortening the fatty acids chain which could be exported to the cytosol for Nmyristoylation of the viral proteins VP2 and VP6 of rotavirus [108] .

Studies on HIV suggested an interaction between viral Nef protein and the peroxisomal enzyme thio-esterase using yeast two hybrid system [122] . Further studies reported an increase in the enzymatic activity of human acyl-coA thio-esterase 3 on binding with the Nef protein [123] . The increased activity of the peroxisomal enzyme was speculated to contribute in alteration of the subcellular morphology and in downregulation of the host antiviral response [108] .

Extensive modifications of proteins for proper functioning and targeting in a cell takes place at the Golgi apparatus. Other functions of Golgi inevitable for the cell are carbohydrate synthesis and lipid transport. The unique stacked structural organization of the Golgi is essential for these functions (Fig. 1) .

The golgi apparatus is composed of three regions namely cis golgi network (CGN), medial and trans golgi network (TGN). Various viruses and viral proteins have been identified to localize to these golgi regions during their life cycle. For example, HeLa cells upon infection with adeno-associated virus type 5 (AAV-5) led to an accumulation of the viral particles in the TGN and in the golginetwork associated coated vesicles [124] . In SARS-CoV, the transmembrane domain of the ORF7B protein contains the retention signal required for accumulation of the protein in the CGN and TGN [125] . Reports suggest bunyaviruses assemble in the Golgi as a result of its retention signal in the glycoprotein (Gn) of the virus [82, 126] .

Fragmentation of golgi body is a common phenomenon that occurs as a result of various viral infections (Fig. 2) . Orf virus (a parapox virus) causes disruption and fragmentation of golgi in Vero cells. This structural modification affects the late vesicular export machinery and results in downregulation of the host immune response [127] . Similar phenomenon was also reported upon expression of 3C protease of foot-and-mouth disease virus in Vero cells [128] . Infection of HRV1A on WI-38, 293T, and H1-HeLa cells was reported to induce fragmentation of golgi body, rearrangement of the golgi membranes into vesicles which are utilized as sites of RNA replication [129] . Another incidence of the virus induced golgi body fragmentation was observed upon infection of SARS-CoV that resulted in death of Vero cells [130] .

Many RNA viruses were also found to alter the integrity of Golgi complex of the host cells. For example, the expression of N-terminal non-structural protein of Norwalk virus in Crandell-Rees feline kidney (CRFK) and HeLa cells co-localizes to Golgi complex and induces its disassembly into discrete aggregates [131] . Another example is the PV infection on Vero cells which results in complete disruption of the CGN into fragments scattered throughout the cytoplasm. The expression of PV protein 2B in Vero, normal rat kidney (NRK) and COS-7 cells also resulted in Golgi bodies disassembly [132] . Similarly, expression of protein 3A of avian encephalomyelitis virus (AEV) in chick embryo brain (CEB) cells and COS-7 cells resulted in depletion of Golgi stacks and in severe disassembly of Golgi bodies [133] .

An interesting alteration in the morphology of golgi apparatus was observed upon infection of Turnip Mosaic Virus (TuMV) on N. benthamiana plant. TuMV infection was observed to induce amalgamation of golgi apparatus, ER and chloroplast [134] .

McCoy mouse fibroblast cells led to accumulation of golgin-97 a TGN resident protein in the viral factories [135] . Similarly, 3A protein of some picornaviruses were also found to interact with a Golgi apparatus resident protein namely golgi adaptor protein acyl coenzyme A (acyl-CoA) binding domain protein 3 (ACBD3/GPC60), acts as an adaptor to recruit phosphatidylinositol 4-kinase class III beta (PI4KIII) in infected cells [136] . Evidence shows that the tomato spotted wilt virus (TSWV) glycoprotein Gn localizes to Golgi membranes and induces deformation of the membranes into pseudo-circular and pleomorphic structures in tobacco plant cells [137] . Upon infection of HeLa cells, rabbit kidney cells and mouse monocytes-macrophages cell lines with VACV, viral progeny becomes enwrapped in the membrane derived from TGN cisterna to form the enveloped virus [138] .

Several viral proteins localize to the golgi body and mature by undergoing post translational modifications such as glycosylation, phosphorylation, etc. Rubella virus was reported to undergo a golgi dependent maturation upon infection of BHK-21 and Vero cells [139] . The inner tegument protein pUL37 of the DNA virus HSV was identified to be responsible in directing the viral capsids to the TGN in order to undergo secondary envelopment in different cell lines [140] . The glycoproteins of Bunyamwera virus undergo primary maturation by modifying their sugar composition in the TGN upon infection of the BHK-21 and Vero cells [141] .

Lipid droplets are single membrane bound organelles with a lipid core that primarily consists of neutral lipids like triacylglycerols (Fig. 1) . They are essential for lipid storage and metabolism in a cell. These stored lipids can be used to generate and maintain energy homeostasis and hence they are central to the cellular function.

Lipid droplets are dynamic intracellular organelles which are required for storing lipids in a cell. They play a major role in energy homeostasis and membrane trafficking [142] . Many RNA viruses exploit this energy storing capacity of lipid droplets to facilitate their replication [142] . Upon expression, various viral proteins are reported to localize to the lipid droplets [143] . For example, upon HCV infection, the HCV NS5A protein localizes to the surface of the lipid droplets with the help of a host factor diacylglycerol acyltransferase 1 (DGAT1) in Huh7 and HEK293T cells [143] . Another study reported that HCV core 3A protein is involved in downregulating the expression of phosphoinositide 3-kinase (PI3K)/phosphatase and tensin (PTEN) which in turn induces the accumulation of enlarged lipid droplets in human Huh7 and HepG2 cells [144] . In another example, DENV C protein was reported to bind and interact with perilipin 3 a protein present on the surface of the lipid droplets in HepG2 cell lines [145] . A similar localization of DENV C protein was also observed upon infection of DENV2 in BHK-21, HepG2, and C6/36 HT mosquito cells of A. albopictus [146] . Additionally, the DENV C protein localization on lipid droplets was also found to be essential for the DENV2 replication [146] .

DENV induces autophagy and results in a reduction in lipid droplet area in Huh7.5 cells, a subline derived from Huh7 cells [147, 148] . Further analysis of the infected cells showed reduced levels of triglycerides in the lipid droplets and suggests that ATP generation by b-oxidation of fatty acids is essential for robust replication of viral RNA [147, 148] . Another study reports that rotavirus recruits lipid droplets into their viroplasm compartments upon infection of MA104, Caco-2, BSC-1, and Cos-7 cell lines [149] . Confocal microscopy studies reported that two LD-associated proteins namely perilipin A and ADRP colocalize with rotaviral proteins present in the viroplasm [149] . Overexpression of the HBV X (HBx) protein was found to induce lipid accumulation in hepatic cells [150, 151] . Na and colleagues found that HBx induces a pathway that involves the expression of Liver X receptor and its associated genes result in accumulation of lipid droplets in HepG2 cell lines [152] .

Lysosomes are single membrane-bound organelles which house enzymes involved in the degradation of various extracellular and intracellular macromolecules such as proteins, pathogens, etc through phagocytic or autophagic pathway. Plant and fungal vacuoles have similar degradative and storage functions like the lysosomes (Fig. 1) . The specialized acidic lumen is the unique feature of these organelles which is needed to keep the enzymes active.

Viruses utilize lysosomal enzymes in order to facilitate their replication and release within the host cell [153] . It has been suggested that lysosomal enzymes are involved at different stages of VACV and mouse hepatitis virus replication [153] . They proposed a possibility for viruses to recruit lysosomal enzymes inside phagosomes in order to uncoat and release their genome in the host cell. A possible role for the lysosomal enzymes in enhancement of glycolysis in viral infected cells was also proposed. Recent studies reported the accumulation of HAV progeny in the lysosome of the host HepG2 cells. The maturation of these viral particles was reported to be catalysed by the lysosomal protease [154] . SV40 infection in BSC-1 and 3T3 cell lines resulted in swelling up of lysosomes followed by the release of lysosomal enzyme into the cytoplasm [155] .

Since lysosomes play a major role in the host's antiviral response, they are likely to become a target for certain viruses. The X protein of the HBV leads to inhibition of lysosomal acidification leading to loss of functioning [156] . However, the lysosome's ability to fuse with autophagosomes was found to remain unaffected. This virus induced accumulation of immature lysosomes resulting in the suppression of autophagic degradation was followed by development of HBV-associated hepatocellular carcinoma [156] . Deglycosylation of the lysosome-associated membrane proteins by neuraminidase (NA) of H5N1 influenza virus resulted in destruction of lysosomes. This was followed by cell death due to the release of hydrolytic lysosomal enzymes to the cytoplasm [157] . Shubin and colleagues studied the expression of 3C protease of HAV in A549 and human lung epidermoid carcinoma (Calu-1) cell lines and found that HAV 3C protease induces the development of non-acidic cytoplasmic vacuoles which originate from several types of lysosomal/endosomal organelles [158] . Similarly several viruses like HIV, adenovirus, PV have been reported to cause lysosomal rupture [159] .

Tobacco plant when infected with cucumber mosaic virus (CMV), the viral replicase complex that constitutes the replicaseassociated protein CMV1a and RNA dependent RNA polymerase protein CMV2a was reported to localize on the vacuolar membrane [160] . Singapore grouper iridovirus (SGIV) infection on grouper embryonic cells (GECs) from the brown-spotted grouper Epinephelus tauvina results in the formation of a large intracellular vacuole for viral accumulation. Later, the virus recruits the host cytosolic membrane-bending proteins in order to induce tubulation of vacuolar membrane [161] . The individual vacuoles fuse together to form a large vacuole which in turn fuses with the cell membrane. These events aid in the release of virions [161] .

Semliki Forest Virus (SFV) targets the vacuolar ATPase in order to cause acidification of vacuoles resulting in low intra luminal pH [162] . Upon infection with the SFV the endocytic vacuoles with low pH trigger membrane fusion essential for the viral pathogenesis in BHK-21 cells [163] . Vacuolar proton ATPase activity leading to low intra endosomal pH was reported to be required for the entry of reovirus into the host cells [164] . Acidification of vacuoles by cellular V-ATPase in human dermal fibroblast cells upon infection of HCMV was reported to be required for the formation of the specialized compartment for virion assembly [165] .

Apart from the above discussed well defined organelles of a cell, viruses also modify and hijack various vesicular structures and protein complexes of the host cell to ensure efficient infection. We discuss these essential compartments/structures in this section. Endosomes are required for internalization of extracellular material into the cells and lead them to lysosomes for degradation or recycle back to the plasma membrane. Multi vesicular bodies are vesicular compartment of the endocytic pathway and contain intraluminal vesicles. Autophagosomes are double membrane vesicular structures that sequester the cytoplasm containing proteins, organelles, etc and direct them to degradation (Fig. 1) .

Efficient cellular entry of most viruses is via endocytic pathway that comprises of various endosomes. Several viruses like influenza, SFV, VSV, SV40, ebola, etc use different endocytic pathways like clathrin, caveoli or micropinocytosis to gain entry into the cells [6,166e168] . Viruses modify or induce the formation of vesicles like endosomes in order to facilitate their multiplication inside the host cells [169] . SFV modifies the endosomal and lysosomal membrane of the infected BHK-21 cells for the construction of its replication site [170] . Further the endosomes and lysosomes were reported to fuse together resulting in the formation of cytoplasmic vacuoles [170] . SV40 was reported to trigger the formation of endocytic vacuoles that migrate and fuse with the nuclear membrane upon infection of CV-1 cells leading to the migration of virions into the infected cell nucleus [171, 172] .

Endosomal sorting complexes required for transport (ESCRT) catalyse the process of invagination of endosomal membrane and result in the formation of multiple vesicular bodies (MVB) in eukaryotic cells [173] . MVB act as an intermediate for transporting ubiquitinated or misfolded protein to lysosomes [173] . MVB are also reported to play an active role in endolysosomal transport and budding of the virus. Several RNA and DNA viruses hijack the ESCRT machinery in order to facilitate their release from the infected cells [169] . The matrix protein VP40 recruits TSG101 protein and ESCRT-1 complex constituting of VPS28, VPS37B and VPS4 in order to direct the ebola virus into multivesicular bodies that assists in their budding [174] . Hoffmann and colleagues reported that upon infection of hepatoma derived cell lines by the DNA virus HBV, cellular a-taxilin acts as an adaptor for the binding of large HBV surface antigen with ESCRT components. This aids in recruiting the ESCRT machinery for the release of HBV-DNA containing particles [175] .

Various RNA viruses alter autophagosomes and induce or suppress autophagy in order to complete their life cycle or to escape from the host antiviral response [176] . It has been reported that the coxsackie B3 infection triggers the formation of autophagosomes in HeLa and HEK293 cells [177] . Prevention of lysosomal fusion with autophagosomes also enhanced coxsackie virus replication in the host cells. Wild type mouse embryonic fibroblast (MEF) and Huh7 cells also exhibit enhanced autophagosome formation upon DENV 2 infection [178] . The viruses modulating the phenomenon of cellular autophagy for their advantage have been reviewed elsewhere [176] .

Proteasome is a complex of proteases that selectively degrades intracellular proteins. This complex is tightly regulated and identifies polyubiquitinated proteins for degradation process. Recent studies identified that viruses hijack UPS in several ways to enhance their infectivity [179] . This is achieved by degradation of host proteins of UPS, enhancing the function of viral proteins by modifications, hampering the modifications of signalling molecules of innate immunity, etc [179] . Virus induced ubiquitination and subsequent proteasomal degradation of p53 as a strategy is employed by DNA viruses such as HPV, AdV, etc [180] . Viral protein X of HIV-2 was reported to be responsible for the ubiquitination and proteasomal degradation of the host protein SAMHD1 that inhibits HIV infection [181] . An interesting strategy by DenV was reported where the viral protein NS5 stimulates proteasomal degradation of STAT2 and blocks type 1 IFN signalling and thus evades the host immune mechanisms [182] . Similarly selective degradation of NS3 (non-structural protein) of the Zika virus via proteasome mediated pathway was recently reported [183] . This proteasome dependant degradation of the viral protein was proposed as a strategy for the host antiviral mechanism.

A role for UPS has also been reported in plant viral infections. Components of RNA silencing such as ARGONAUTE 1 are targeted to proteasomal degradation by viruses like Potato virus X, Enamovirus, etc for efficient infection [184, 185] .

This review summarizes the modifications that organelles encounter upon viral infection in a cell. Understanding organelle dynamics under various conditions is a fundamental question that has attracted researchers for a long time. The importance of organelle dynamics and function is highlighted by many examples of diseases/disorders where it is affected. Alterations in organelles such as shape, content, dynamics and eventually the function as a result of viral infections is observed. Not only viruses but pathogenic bacteria have also been reported to alter organelles for their survival and infection. As emphasized in this paper, recent studies have shown that many viruses encode proteins that are targeted to various cellular organelles and control their functions. Certainly there exists a close relationship between organelle dynamics and viral infections but thorough characterization will highlight their relevance to pathogenesis. Advanced methods in microscopy and proteomics have enabled such characterization and the molecular details of virus-host interactions and viral replication in host cells is now understood in detail for few viruses. It is important to determine how various organelle proteins are temporally and spatially regulated upon viral infections leading to altered functions. Organelles not as independent entities but a role for inter-organelle communication/inter-organelle cross talk in a cell for optimum functioning is now unequivocally accepted. This is another very interesting aspect to be explored to enhance our understanding of the virus-host interaction mechanisms to enable design of new antiviral strategies. Our understanding on the organelle-virus interaction has been rapidly increasing with the advent of new molecular biology tools and advance imaging techniques. Although we know the basic modus operandi of the viruses, there might be a novel virus that behaves different than the existing dogma with respect to host cellular architecture.

The authors declare to no conflict of interest.

Ground control to major TOM: mitochondria-nucleus communication

The upsides and downsides of organelle interconnectivity

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

HIV-1 and the host cell: an intimate association

Virulence and pathogenesis

Virus entry by endocytosis

Signaling organelles of the innate immune system

Lipid droplet density alters the early innate immune response to viral infection

Virus factories: associations of cell organelles for viral replication and morphogenesis

Exploring and exploiting proteome organization during viral infection

Nuclear remodelling during viral infections

How viruses access the nucleus

The road to chromatin -nuclear entry of retroviruses

Integration of murine leukemia virus DNA depends on mitosis

Two nuclear localization signals in the HIV-1 matrix protein regulate nuclear import of the HIV-1 pre-integration complex

Characterization of HIV-1 vpr nuclear import: analysis of signals and pathways

HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway

Integrase interacts with nucleoporin NUP153 to mediate the nuclear import of human immunodeficiency virus type 1

Nuclear import and export of influenza virus nucleoprotein

Application of bioinformatics-coupled experimental analysis reveals a new transport-competent nuclear localization signal in the nucleoprotein of influenza A virus strain

Importin alpha nuclear localization signal binding sites for STAT1, STAT2, and influenza A virus nucleoprotein

Function of dynein and dynactin in herpes simplex virus capsid transport

Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus

Herpes simplex virus type 1 entry into host cells: reconstitution of capsid binding and uncoating at the nuclear pore complex in vitro

Import of adenovirus DNA involves the nuclear pore complex receptor CAN/Nup214 and histone H1

Nucleoporin 153 arrests the nuclear import of hepatitis B virus capsids in the nuclear basket

Phosphorylationdependent binding of hepatitis B virus core particles to the nuclear pore complex

Nuclear import of hepatitis B virus capsids and release of the viral genome

Role of nuclear pore complex in simian virus 40 nuclear targeting

Pushing the envelope: microinjection of minute virus of mice into Xenopus oocytes causes damage to the nuclear envelope

Parvoviral nuclear import: bypassing the host nuclear-transport machinery

Nucleoli: composition, function, and dynamics

Involvement of UL24 in herpes-simplex-virus-1-induced dispersal of nucleolin

Involvement of the UL24 protein in herpes simplex virus 1-induced dispersal of B23 and in nuclear egress

Adenovirus core protein V is delivered by the invading virus to the nucleus of the infected cell and later in infection is associated with nucleoli

Adenovirus protein V induces redistribution of nucleolin and B23 from nucleolus to cytoplasm

Effects of adenovirus infection on rRNA synthesis and maturation in HeLa cells

Encephalomyocarditis virus (EMCV) proteins 2A and 3BCD localize to nuclei and inhibit cellular mRNA transcription but not rRNA transcription

Rhinovirus 3C protease precursors 3CD and 3CD' localize to the nuclei of infected cells

The post-transcriptional regulator Rev of HIV: implications for its interaction with the nucleolar protein B23

Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division

Inhibition of nuclear import and alteration of nuclear pore complex composition by rhinovirus

Nucleolin stimulates viral internal ribosome entry site-mediated translation

Quantitative proteomic analysis of A549 cells infected with human respiratory syncytial virus

IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis

HSV-1 IE protein Vmw110 causes redistribution of PML

Mediation of epstein-barr virus EBNA-LP transcriptional coactivation by Sp100

Adenovirus replication is coupled with the dynamic properties of the PML nuclear structure

Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response

Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression

Two RING finger proteins, the oncoprotein PML and the arenavirus Z protein, colocalize with the nuclear fraction of the ribosomal P proteins

SUMOylation promotes PML degradation during encephalomyocarditis virus infection

Rabies virus P and small P products interact directly with PML and reorganize PML nuclear bodies

Viral interactions with the nuclear transport machinery: discovering and disrupting pathways

Remodelling of the nuclear lamina during human cytomegalovirus infection: role of the viral proteins pUL50 and pUL53

Papillomavirus interaction with cellular chromatin

Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus

Wrapping membranes around plant virus infection

Inhibition of sterol biosynthesis reduces tombusvirus replication in yeast and plants

Endoplasmic reticulum: the favorite intracellular niche for viral replication and assembly

Direct formation of vaccinia virus membranes from the endoplasmic reticulum in the absence of the newly characterized L2-interacting protein A30.5

Intracellular localisation of dengue-2 RNA in mosquito cell culture using electron microscopic in situ hybridisation

Composition and three-dimensional architecture of the dengue virus replication and assembly sites

Cellular origin and ultrastructure of membranes induced during poliovirus infection

Remodeling the endoplasmic reticulum by poliovirus infection and by individual viral proteins: an autophagylike origin for virus-induced vesicles

Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex

SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum

Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes

The potato virus X TGBp2 movement protein associates with endoplasmic reticulum-derived vesicles during virus infection

Tombusviruses upregulate phospholipid biosynthesis via interaction between p33 replication protein and yeast lipid sensor proteins during virus replication in yeast

Opportunistic intruders: how viruses orchestrate ER functions to infect cells

Arms race between enveloped viruses and the host ERAD machinery

Mutational analysis of glycosylation, membrane translocation, and cell surface expression of the hepatitis E virus ORF2 protein

Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum

The expanding roles of endoplasmic reticulum stress in virus replication and pathogenesis

BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol

Global sitespecific N-glycosylation analysis of HIV envelope glycoprotein

The interplay between mitochondrial dynamics and mitophagy

Mitochondrial fusion, fission, and mitochondrial toxicity

Mitochondrial dynamics and viral infections: a close nexus

Hepatitis B virus disrupts mitochondrial dynamics: induces fission and mitophagy to attenuate apoptosis

SARScoronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome

Mitophagy in viral infections

The matrix protein of human parainfluenza virus type 3 induces mitophagy that suppresses interferon responses

Mitophagy promotes replication of oncolytic newcastle disease virus by blocking intrinsic apoptosis in lung cancer cells

Viruses as modulators of mitochondrial functions

Hepatitis B virus x protein induces perinuclear mitochondrial clustering in microtubule-and dyneindependent manners

Migration of mitochondria to viral assembly sites in African swine fever virus-infected cells

Herpes simplex virus eliminates host mitochondrial DNA

Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation

Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores

The coxsackievirus 2B protein suppresses apoptotic host cell responses by manipulating intracellular Ca2þ homeostasis

Role of Ca2þin the replication and pathogenesis of rotavirus and other viral infections

Human hepatitis B virus-X protein alters mitochondrial function and physiology in human liver cells

HBx sensitizes cells to oxidative stress-induced apoptosis by accelerating the loss of Mcl-1 protein via caspase-3 cascade

Influence of cytosolic and mitochondrial Ca2þ, ATP, mitochondrial membrane potential, and calpain activity on the mechanism of neuron death induced by 3-nitropropionic acid

Viral product trafficking to mitochondria, mechanisms and roles in pathogenesis

A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection

The myxoma poxvirus protein, M11L, prevents apoptosis by direct interaction with the mitochondrial permeability transition pore

The HIV-1 viral protein R induces apoptosis via a direct effect on the mitochondrial permeability transition pore

A renewed focus on the interplay between viruses and mitochondrial metabolism

Systemslevel metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

Dynamics of the cellular metabolome during human cytomegalovirus infection

Glycolysis during early infection of feline and human cells with feline leukemia virus

Glycolysis in chick embryo cell cultures transformed by Rous sarcoma virus

Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism

Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production

Viruses exploiting peroxisomes

Import of peroxisomal matrix and membrane proteins

Peroxisomes are platforms for cytomegalovirus' evasion from the cellular immune response

Expression of the cymbidium ringspot virus 33-kilodalton protein in Saccharomyces cerevisiae and molecular dissection of the peroxisomal targeting signal

Localization of the tomato bushy stunt virus replication protein p33 reveals a peroxisome-to-endoplasmic reticulum sorting pathway

The host Pex19p plays a role in peroxisomal localization of tombusvirus replication proteins

A key role for heat shock protein 70 in the localization and insertion of tombusvirus replication proteins to intracellular membranes

The pestivirus N terminal protease N(pro) redistributes to mitochondria and peroxisomes suggesting new sites for regulation of IRF3 by N(pro.)

The fine structure of cymbidium ringspot virus infections in host tissues. III. Role of peroxisomes in the genesis of multivesicular bodies

The role of the p33:p33/p92 interaction domain in RNA replication and intracellular localization of p33 and p92 proteins of cucumber necrosis tombusvirus

Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism

Micro-RNAs upregulated during HIV infection target peroxisome biogenesis factors: implications for virus biology, disease mechanisms and neuropathology

Flavivirus infection impairs peroxisome biogenesis and early antiviral signaling

Identification of a type 1 peroxisomal targeting signal in a viral protein and demonstration of its targeting to the organelle

Binding of HIV-1 Nef to a novel thioesterase enzyme correlates with Nef-mediated CD4 down-regulation

A novel acyl-CoA thioesterase enhances its enzymatic activity by direct binding with HIV Nef

Endocytosis of adeno-associated virus type 5 leads to accumulation of virus particles in the golgi compartment

The transmembrane domain of the severe acute respiratory syndrome coronavirus ORF7b protein is necessary and sufficient for its retention in the golgi complex

A signal for golgi retention in the bunyavirus G1 glycoprotein

Orf virus interferes with MHC class I surface expression by targeting vesicular transport and golgi

Foot-and-mouth disease virus 3C protease induces fragmentation of the golgi compartment and blocks intra-golgi transport

Fragmentation of the golgi apparatus provides replication membranes for human rhinovirus 1A

The open reading frame 3a protein of severe acute respiratory syndrome-associated coronavirus promotes membrane rearrangement and cell death

Norwalk virus N-Terminal nonstructural protein is associated with disassembly of the golgi complex in transfected cells

Poliovirus infection and expression of the poliovirus protein 2B provoke the disassembly of the golgi complex, the organelle target for the antipoliovirus drug Ro-090179

Membrane-association properties of avian encephalomyelitis virus protein 3A

Impact on the endoplasmic reticulum and golgi apparatus of turnip mosaic virus infection

A trans-golgi network resident protein, golgin-97, accumulates in viral factories and incorporates into virions during poxvirus infection

The 3A protein from multiple picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIbeta

Tomato spotted wilt virus glycoproteins induce the formation of endoplasmic reticulum-and golgi-derived pleomorphic membrane structures in plant cells

Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans golgi network

Structural maturation of rubella virus in the golgi complex

Inner tegument protein pUL37 of herpes simplex virus type 1 is involved in directing capsids to the trans-golgi network for envelopment

Key golgi factors for structural and functional maturation of bunyamwera virus

Emerging role of lipid droplets in host/pathogen interactions

Lipid droplets and viral infections

Down-regulation of phosphatase and tensin homolog by hepatitis C virus core 3a in hepatocytes triggers the formation of large lipid droplets

Dengue virus capsid protein binding to hepatic lipid droplets (LD) is potassium ion dependent and is mediated by LD surface proteins

Dengue virus capsid protein usurps lipid droplets for viral particle formation

Dengue virus-induced autophagy regulates lipid metabolism

Dengue virus and autophagy

Rotaviruses associate with cellular lipid droplet components to replicate in viroplasms, and compounds disrupting or blocking lipid droplets inhibit viroplasm formation and viral replication

Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRalpha

Hepatitis B virus X protein induces hepatic steatosis via transcriptional activation of SREBP1 and PPARgamma

Liver X receptor mediates hepatitis B virus X protein-induced lipogenesis in hepatitis B virusassociated hepatocellular carcinoma

Activation of lysosomal enzymes in virus-infected cells and its possible relationship to cytopathic effects

Lysosomes serve as a platform for hepatitis A virus particle maturation and nonlytic release

Lysosomal changes in lytic and nonlytic infections with the simian vacuolating virus (SV40)

Hepatitis B virus X protein inhibits autophagic degradation by impairing lysosomal maturation

Neuraminidase of influenza A virus binds lysosome-associated membrane proteins directly and induces lysosome rupture

Protease 3C of hepatitis A virus induces vacuolization of lysosomal/endosomal organelles and caspase-independent cell death

Lysosomal cell death at a glance

A zinc finger protein Tsip1 controls cucumber mosaic virus infection by interacting with the replication complex on vacuolar membranes of the tobacco plant

Visualization of assembly intermediates and budding vacuoles of Singapore grouper iridovirus in grouper embryonic cells

Involvement of the vacuolar H(þ)-ATPase in animal virus entry

Membrane and protein interactions of a soluble form of the semliki forest virus fusion protein

The entry of reovirus into L cells is dependent on vacuolar proton-ATPase activity

Cellular v-ATPase is required for virion assembly compartment formation in human cytomegalovirus infection

Endocytosis via caveolae

Endocytosis of simian virus 40 into the endoplasmic reticulum

Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes

Membrane dynamics associated with viral infection

Biogenesis of the semliki forest virus RNA replication complex

Fusion of SV40-induced endocytotic vacuoles with the nuclear membrane

Interaction of endocytotic vacuoles with the inner nuclear membrane in simian virus 40 entry into CV-1 cell nucleus

ESCRT complexes and the biogenesis of multivesicular bodies

Involvement of vacuolar protein sorting pathway in ebola virus release independent of TSG101 interaction

Identification of alpha-taxilin as an essential factor for the life cycle of hepatitis B virus

Divergent roles of autophagy in virus infection

Autophagosome supports coxsackievirus B3 replication in host cells

Autophagic machinery activated by dengue virus enhances virus replication

iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING

Identification of three functions of the adenovirus e4orf6 protein that mediate p53 degradation by the E4orf6-E1B55K complex

Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx

NS5 of dengue virus mediates STAT2 binding and degradation

Viperin restricts zika virus and tick-borne encephalitis virus replication by targeting NS3 for proteasomal degradation

The silencing suppressor P25 of potato virus X interacts with argonaute1 and mediates its degradation through the proteasome pathway

The enamovirus P0 protein is a silencing suppressor which inhibits local and systemic RNA silencing through AGO1 degradation

We sincerely apologize to our colleagues for any research study or review publication not being cited in this review. This is only due to space limitation. Research in the laboratory of SN is supported by grants from Science and Engineering Research Board (