key: cord-0854955-3r1ijafm
authors: Nevers, Quentin; Albertini, Aurélie A.; Lagaudrière-Gesbert, Cécile; Gaudin, Yves
title: Negri bodies and other virus membrane-less replication compartments()
date: 2020-08-21
journal: Biochim Biophys Acta Mol Cell Res
DOI: 10.1016/j.bbamcr.2020.118831
sha: aa43180ea5bd68029968cac66e6fd093b1e7f9d9
doc_id: 854955
cord_uid: 3r1ijafm

Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place in viral factories where specific viral and cellular proteins as well as nucleic acids concentrate. Viral factories can be either membrane-delimited or devoid of any cellular membranes. In the latter case, they are referred as membrane-less replication compartments. The most emblematic ones are the Negri bodies, which are inclusion bodies that constitute the hallmark of rabies virus infection. Interestingly, Negri bodies and several other viral replication compartments have been shown to arise from a liquid-liquid phase separation process and, thus, constitute a new class of liquid organelles. This is a paradigm shift in the field of virus replication. Here, we review the different aspects of membrane-less virus replication compartments with a focus on the Mononegavirales order and discuss their interactions with the host cell machineries and the cytoskeleton. We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells.

During their replication cycle, many viruses induce the formation of specialized intracellular compartments in the host cell. These structures often referred as viral inclusions, viral factories or viroplasms, concentrate viral proteins, nucleic acids and specific cellular factors. In many cases, those viro-induced compartments harbor essential steps of the viral cycle and constitute a platform facilitating viral replication and assembly but also protecting the viral genome from cellular defense mechanisms. Such viral factories have been now identified for a variety of non-related viruses [1] [2] [3] .

Viral factories are very heterogeneous. They can be associated with membranes from diverse organelles (mainly endoplasmic reticulum -ER-, late endosomes, lysosomes, and mitochondria) that they rearrange. This is the case for positive-strand RNA viruses leading to the formation of double-membrane vesicles (Coronaviridae, Arteriviridae, Picornaviridae and Flaviviridae) or spherules derived from diverse cellular membranes (Togaviridae, Nodaviridae and Flaviviridae) (Fig. 1 ).

However, for several negative-strand RNA, double stranded RNA and DNA viruses, viral factories are devoid of membranes. These compartments can be either cytosolic or nuclear and, in several instances, have been demonstrated to have properties like those of liquid organelles (Fig. 1 ).

Membrane-less liquid organelles contribute to the compartmentalization of the eukaryotic cell interior [4] [5] [6] [7] . They are referred as droplet organelles, proteinaceous membrane-delimited organelles. Finally, they are highly enriched in some proteins that are much more concentrated in those structures than in the cytosol, as a result of liquid-liquid phase separation (LLPS) [7] . With the rapid identification of cellular membraneless compartments and proteins that undergo LLPS in vitro, a major challenge in the field is to demonstrate unambiguously that a specific structure is indeed a phase-separated liquid body in the cellular context. Currently, common criteria for defining such a structure are that it is spherical, fuses, reversibly deforms when encountering a physical barrier, and recovers from photobleaching [14] .

Here, we will review membrane-less viral compartments with a focus on those that have liquid organelles properties. We will discuss their composition and their interactions with the host cell machineries, particularly those of the innate immune system, of which several components also form membrane-less condensates in infected cells, and of the cytoskeleton.

Mononegavirales (MNV) constitute a viral order which contains several viruses causing important human diseases (including Rabies virus -RABV-, Ebola virus -EBOV-, measles virus -MeV-, mumps virus -MuV-, human respiratory syncytial virus -RSV-). Their genome consists of a negative sense, single-stranded RNA molecule ranging from 10 to 15 kb, starting and ending with a non-coding leader and trailer sequence, respectively. The viral RNA is tightly associated with the nucleoprotein (N or NP) to form the helical ribonucleoprotein (RNP) (Fig. 2) . The RNP recruits the viral RNA-dependent RNA polymerase (RdRp) complex, composed of the protein L (the polymerase which bears polyribonucleotidyltransferase and methyltransferase activities) and its non-enzymatic J o u r n a l P r e -p r o o f cofactors (P for rhabdoviruses, paramyxoviruses, and pneumoviruses, VP35 for filoviruses), to form the nucleocapsid. In the nucleocapsid, P acts as a tether between L and the RNP. The nucleocapsid is enwrapped by a lipid bilayer that is derived from a host cell membrane during the budding process. The matrix protein (M, VP40 for filoviruses) is located beneath the viral membrane and bridges the RNP and the lipid bilayer, which contains one or two transmembrane glycoproteins that are involved in viral entry.

The cell cycle of MNV is entirely cytoplasmic (with the notable exception of that of the Bornaviridae family members). The negative sense RNP, once released in the cytoplasm, constitutes the template for viral gene expression and replication by the RdRp complex. In this complex, P is bridging L and the template-associated nucleoproteins. Transcription begins at the 3' end of the genomic RNA and results in the synthesis of a positive, uncapped and short leader RNA and capped and polyadenylated messenger RNAs (mRNAs). Viral mRNAs are then translated by the host cell translation machinery providing a source of N protein necessary to encapsidate the nascent RNA. This results in the switch of the activity of the RdRp complex from transcription to replication to produce RNPs containing full-length antigenomic RNA (positive sense), which in turn serve as templates for the synthesis of genomic RNA (negative sense). During the replication stage, when not bound to the viral genomic or antigenomic RNA, N is kept soluble by binding the amino-terminal region of P thus forming the so-called N 0 P complex (Fig. 2B, 2D ) [15] [16] [17] . [34] are spherical (at least during the initial stages of infection), suggesting that they could be liquid organelles formed by phase separation. This liquid nature was confirmed by live-cell imaging for RABV [30] , VSV [31] and MeV [25].

First, it was shown that when two spherical inclusions contact one another, they readily fuse and round up into a single larger spherical one [25, 30, 31] . They also reversibly deform when encountering a physical barrier and disappear when exposed to an osmotic shock [30] . 

Beyond the MNV order, IBs are also observed during segmented negative strand RNA virus infections. Indeed, it has been shown that cells infected by influenza A virus contain inclusions located in the vicinity of the ER exit site. These inclusions, which have been proposed to be involved in the control of the assembly process, have liquid properties [35] .

Similarly, the spherical aspect of the granules which concentrate the three Bunyavirus genome segments [36] suggest the possibility that they also have liquid properties.

Co-expression of N and P proteins of paramyxoviruses and RABV after cell transfection also leads to the formation of spherical inclusions [25, 30, 37, 38] . In the case of VSV, the presence of L protein is also required for such inclusions to be formed [31] whereas in the case of EBOV, NP alone is sufficient for IB generation [39] . For both RABV and MeV, the N-P inclusions formed in this minimal system have the same liquid characteristics as the viral factories [25, 30] . In the other cases, the spherical aspect of the inclusions is a strong argument in favor of their liquid nature, but additional experiments are necessary to definitively conclude on this point.

RABV and MeV minimal systems were used to identify P and N domains that are essential for inclusion formation. The phosphoprotein of paramyxoviruses and rhabdoviruses share a common modular organization [40] [41] [42] (Fig. 3) . The N-terminal part of the protein is involved in the formation of the N 0 P complex [43] [44] [45] (Fig. 2B, 2D , 3C) and, for rhabdoviruses, in the interaction with the L protein [46, 47] (Fig. 3B, 3D ). The C-terminal domain (PCTD for RABV and VSV, XD for MeV) binds N associated with RNA [48] [49] [50] ( Fig. 3) . The XD domain of paramyxoviruses can also bind L [51] . Two central intrinsically J o u r n a l P r e -p r o o f disordered domains (IDD1 and IDD2 for RABV, P tail and P loop for MeV) are flanking an oligomerization domain. Rhabdovirus P is dimeric in solution [52, 53] (Fig. 3B , 3C) whereas paramyxovirus P form tetramers [54] (Fig. 3E ). Despite the absence of sequence similarity and the differences in the domain structures (Fig. 3) , for both RABV and MeV P, it has been shown that the oligomerization domain, the second intrinsically disordered domain (IDD2 / More recently, it has been shown that MeV N (produced in association with the 50 first amino-terminal residues of P and thus in the form N 0 P 50 ) and P expressed in E. coli form liquid-like membrane-less organelles upon mixing in vitro under physiological salt and protein concentrations [55] . As in the cell [25], the oligomerization domain, P Loop and XD are required for LLPS. In this system, it was also shown that the interaction between the disordered C-terminal part of N (N Tail residues 400-525) and XD of P is essential for droplet formation. Indeed, a mutation of N (S491L) abrogating the N Tail :PXD interaction and known to significantly decrease viral transcription in vivo resulted in suppression of phase separation.

Finally, when RNA was added, it concentrated in the N-P droplets and was encapsidated by N protomers to form nucleocapsid-like particles. The rate of encapsidation within droplets was enhanced compared to the dilute phase, which suggests a function of LLPS in MeV replication [55] . in the minimal systems in which N is associated with cellular RNAs and forms N-RNA rings and short RNP-like structures [43, 56] ), RNA-binding proteins (N in this case) and proteins containing IDDs (P and sometimes N in this case). For several cellular proteins that phaseseparate, cation-pi interactions between arginine and aromatic residues have been shown to be key in the process [57, 58] . It is not known whether similar residues mediate the weak interactions that drive LLPS for MNV condensates. A comparison between RABV, MeV and EBOV nucleoprotein and phosphoprotein sequences with a focus on their IDDs do not reveal conserved specificities besides a slight enrichment in positive residues in RABV IDD2 and MeV P loop (both required to observe LLPS in the minimal systems) (Table 1) . Furthermore, alignment of the sequences of lyssaviruses phosphoproteins reveal a poor conservation of IDDs compared to the rest of the protein sequence in the viral genus [30].

The first viral factories which were characterized were those of large DNA viruses such as the Poxviridae, the Iridoviridae and the Asfarviridae [59] [60] [61] [62] . Those cytoplasmic factories are devoid of membrane and located near the microtubule organizing center. They have several characteristics reminiscent of those of the cellular aggresomes which concentrate misfolded proteins in the cell [63] . They recruit mitochondria in their vicinity, contain molecular chaperones such as heat-shock proteins (HSP) and are surrounded by a vimentin cage [64] . However, no data are supporting the possible liquid nature of those cytoplasmic structures.

Other DNA viruses belonging to Herpesviridae, Adenoviridae, Parvoviridae, Polyomaviridae and Papillomaviridae families induce the formation of membrane-less assemblies inside the nucleus termed viral replication compartments (or centers), hereafter referred as VRCs [65] , which concentrate viral proteins and nucleic acids, incoming viral genomes and host proteins. Herpesviruses and adenoviruses VRCs also coalesce as infection progresses and can fuse together in a liquid-like manner [66] [67] [68] [69] . However, unlike many other cellular liquid organelles [70] [71] [72] , HSV-1 VRCs are not disrupted by treatment with 1,6hexanediol and a model of their formation, not based on LLPS, has been proposed [69] .

However, sensitivity to hexanediol is insufficient to unequivocally demonstrate that a structure is formed via LLPS [14] and the identification of the physicochemical principles 

Double strand RNA (dsRNA) viruses are also known to induce the formation of membrane-less cytosolic electron-dense inclusions. This is particularly documented for the Reoviridae family of viruses which contain 10 (for reoviruses) or 11 (for rotaviruses) J o u r n a l P r e -p r o o f segments of genomic dsRNA. Those organelles are referred as viroplasms. They constitute the site of viral genome transcription and replication, as well as the site of packaging of the newly synthesized pregenomic RNA segments into the viral cores [75] [76] [77] [78] . Viroplasms appear to be spherical and can fuse together [79, 80] which indicates that they have liquid properties. For rotaviruses, viroplasms are nucleated by two essential non-structural proteins, NSP2 and NSP5, and the inner virion capsid protein VP2, with NSP5 being crucial for both the recruitment of viroplasmic proteins and the architectural assembly of the viroplasms. In non-infected cells, co-expression of NSP5 either with NSP2 or VP2 leads to the formation of viroplasm-like structures [81, 82] . Interestingly, NSP5 shares several characteristics with the phosphoproteins of MNV as it is phosphorylated, forms oligomers and contains intrinsically disordered segments [83] . Similarly, for reoviruses, the expression of the non-structural protein µNS alone leads to the formation of large inclusions that are similar to the viroplasms [84] . However, unlike NSP5, µNS is not predicted to contain long intrinsically disordered segments.

Although the viral factories of positive stand RNA viruses are associated with membranes, several of those viruses also form spherical intracytoplasmic inclusions that might have liquid properties. For example, depending on their genus, coronavirus nucleocapsid proteins (N) can form inclusion either in the cytoplasm [85] or in the nucleus in association with the nucleolus [86, 87] . In keeping with this idea, it has been shown in vitro that the SARS-CoV-2 N protein contains disordered regions and phase separates with RNA [88] [89] [90] [91] . The phase separation is regulated by N phosphorylation [91] . Interestingly, in vitro, N also partitions into liquid phases formed by several human RNA-binding proteins [89] , which is reminiscent of coronavirus N ability to associate with the nucleolus. These Finally, EBOV NP recruits several proteins into the IBs, which include the nuclear RNA export factor NFX1 to drive viral protein synthesis [100] and the histone-lysinemethyltransferase SMYD3 [101] as well as the CAD protein [102] to facilitate mRNA transcription and replication.

Mass spectrometry analyses of pull-down complexes of tagged NSP2 and NSP5 from human rotavirus incubated with extracts from uninfected rotavirus-permissive MA104 cells J o u r n a l P r e -p r o o f revealed the presence of several host heterogeneous nuclear RNPs (hnRNPs) and AU-rich element-binding proteins (ARE-BPs) [103] . Finally, the composition of HSV-1 VRC has been investigated by immunoprecipitation of ICP8 that appears as one of their most important components. This has allowed the identification of more than 50 viral and cellular proteins, mainly involved in DNA replication, DNA repair, chromatin remodelling, transcription, and RNA processing [104] .

In conclusion, although a significant number of proteins have been found associated with viral IBs, the precise role of those associations with, or sequestrations in, IBs or VRCs as well as the underlying molecular mechanisms remain to be determined and will certainly constitute a new field of research in the coming years.

The cytoskeleton plays an important role in the morphogenesis and evolution all along tether cytoplasmic liquid organelles such as P-bodies and drive their fission in an active process [106] . It is not excluded that RABV has hijacked a cellular machinery specifically involved in this process or that the same basic physicochemical principles are at work in both cases. The subtle interplay between viral IBs and innate immunity is particularly exemplified by RABV for which P is not only one of the major component of the NBs but also the major viral counteractant of the innate immune response [108] . First, P has a critical role in suppression of IFN production by blocking the phosphorylation of the transcription factor interferon regulatory factor 3 (IRF-3) [109] . Second, the interaction of P with STAT1 leads to the inhibition of IFN signaling by different processes including inhibition of STAT1-DNA binding [110] and STAT1 sequestration away from the nucleus [111] .

Similarly, EBOV VP35, which is concentrated in the IBs largely counteracts the innate immunity. It binds double-stranded RNA and inhibits IFN production induced by RIG-I signaling [112, 113] , prevents PKR activation [114] and impairs the function of IFN regulatory factor-activating kinases IKK and TBK-1 [115] .

In the case of paramyxoviruses, the proteins that inhibit IFN production and counteract IFN response, although expressed from the P gene, are distinct from P [116] . They are either expressed from an alternate reading frame or from an alternate transcript due to the presence of an editing site. C protein of MeV corresponds to the former case and has a completely different amino-acid sequence from P whereas V protein corresponds to the latter case and has the same amino-terminal part as P but a distinct C-terminal domain. Consequently, V is J o u r n a l P r e -p r o o f missing the P domain required to associate with IBs and V protein has primarily a diffuse nuclear distribution [117] . Therefore, MNV evolved different strategies to counteract innate immunity. Some viruses may sequester the proteins involved in those pathways inside the viral IBs whereas others keep them away from the viral factory.

Several cytosolic sensors of the innate immunity are also associated with liquid organelles. The best characterized of those organelles are the SGs which are formed when the cell is under a cytoplasmic stress. They are storage sites containing translationally silenced mRNPs that can be released to resume translation after the stress subsides. SGs can be induced by viral infections [9, 118] and are thought to have antiviral activities as they contain RIG-I and MDA-5 [119] [120] [121] . Interestingly, during RABV infection, SGs come into close contact with NBs [9] but do not fuse with them [30] . This indicates that NBs and SGs are made of non-miscible liquid phases. However, they exchange some material as the mRNAs (but not the genomes and antigenomes) are transported from NBs, where they are synthesized, into SGs [9] . For VSV, it has been shown that SGs associated proteins such as Poly(RC) Binding Protein 2 (PCBP2), T-cell-restricted intracellular antigen 1 (TIA1), and TIA1-related protein (TIAR) are associated with the viral factories. However, the bona fide SG markers, such as eukaryotic initiation factor 3 (eIF3) or eIF4A were not present in the factory [122] . In accordance with these results, it is worth noting that TIA-1 exerts an antiviral effect on both RABV [9] and VSV [122] .

SGs [123] . However, as infection proceeds, normal SG puncta are disrupted, and SGassociated proteins localized to the periphery of viral factories [124] . SGs alteration is due to J o u r n a l P r e -p r o o f MRV NS protein association with Ras-GAP SH3-binding protein 1 (G3BP1) [124] , a double-stranded nucleic acid helicase which is a master regulator of SG formation [125] . By comparing MRV replication on wild-type and G3BP1 -/-MEFs, it was shown that G3BP1 inhibits viral growth [124] . It has been suggested that G3BP1 relocalization to the viral factory periphery induced by NS induces SG disruption in order to facilitate MRV replication in the host translational shutoff environment [124] . On the other hand, for rotaviruses, which also belong to the Reoviridae family, it appears that most of the main SG components are present in the viroplasms but that there is a selective exclusion of G3BP1.

This sequestration promotes progeny virus production [126] . Taken together, all those examples indicate that there is a general, although remarkably diverse, interplay between SGs and viral factories.

More recently, it has been shown that the cyclic GMP-AMP synthase (cGAS, which leads to the production of the secondary messenger cyclic GMP-AMP), a major sensor of cytosolic DNA from invading viruses which triggers innate immune responses, induced the formation of liquid-like droplets by binding DNA in which cGAS was activated [127] . In a cellular context, the liquid phase separation and the IFN response to intracellular DNA are both dependent on the presence of G3BP1, which binds cGAS. Finally, an RNA-dependent association with PKR promoted the formation of those G3BP1-dependent, membraneless cytoplasmic structures necessary for the DNA-sensing function of cGAS in human cells [128] . Thus, the nucleic acid sensing pathways involved in viral infection detection require the formation of specialized subcellular structures having liquid properties.

Several ISG products also form membrane-less condensates. This is the case of human MxA, a cytoplasmic 70-kDa dynamin-family large GTPase which is induced in cells exposed J o u r n a l P r e -p r o o f to type I and III IFNs and has a broad spectrum of antiviral activities [129] . Even in uninfected cells, MxA forms spherical or irregular bodies of variable size, filaments, and sometimes a reticulated network that reversibly disassemble/reassemble within minutes of sequential decrease/increase, respectively, in tonicity of extracellular medium [71] . Promyelocytic leukemia protein (PML), which is the organizer of the PML nuclear bodies, is also induced by IFN. PML nuclear bodies also contain two other resident proteins, the ISG product Speckled protein of 100 kDa (Sp100) and death-associated dead protein (Daxx), as well as several other proteins transiently recruited in PML bodies in response to different stimuli [130] . PML bodies as other nuclear bodies exhibit liquid-like properties [131, 132] . The initiation of VRCs of DNA viruses occurs at sites near PML-nuclear bodies.

Human papillomavirus (HPV) infection requires the presence of PML protein suggesting that PML bodies are essential to establish infection [133, 134] . However, Sp100 and DAXX, which act as transcriptional repressors, restrict viral gene expression in ADV [135] , HPV [136] , HSV-1 [137] , and HCMV [138] infections. Therefore, it is not surprising that most of the DNA viruses that replicate in the nucleus have evolved strategies to disrupt the PML bodies and to degrade or inhibit their components [138] [139] [140] [141] . As a well-characterized example, incoming HSV-1 genomes transiently co-localize with PML nuclear bodies [142] , which surround and encapsulate incoming viral genomes before being disrupted by newly synthesized ICP0 viral proteins [137, 139, 143] . The antiviral action of PML nuclear bodies is also observed on RNA viruses including dengue virus [144] , influenza virus [145] and rhabdoviruses [146, 147] . Here again, viruses have evolved mechanisms that counteract PML J o u r n a l P r e -p r o o f function. As an example, RABV P interacts with PML and retains it in the cytoplasm to alter PML nuclear bodies [148] and consequently is thought to counteract the antiviral effect of isoform PML IV against RABV [146] .

The discovery that several viro-induced membrane-less compartments have liquid properties and are formed by LLPS is a paradigm shift in the field (Table 2) . Indeed, these compartments provide a functional microenvironment, of which the physicochemical properties remain to be characterized, for the optimal working of the viral replication machinery. Understanding the molecular basis of the weak interactions that keep the cohesion of those compartments might lead to the development of drugs that destabilize the viral factories or that concentrate inside to target the viral enzymes more efficiently.

An exciting field of research is the identification of the proteome of those compartments. Until now, only a few specific cellular factors, which directly interact with viral proteins such as the nucleoproteins and phosphoproteins of MNV, have been shown to concentrate in these structures. The proteome of the viral factories is probably much larger and some proteins might also preferentially partition in the organelle liquid phase due to their physicochemical properties without strongly interacting with any viral protein. As the liquid nature of MNV viral factories precludes their purification, original techniques will be required to map the complete proteome. A promising approach is proximity labeling which has already been used to map the proteome of SGs and processing bodies [125, 149, 150] .

Interactions between viral factories and several cellular components such as the cytoskeleton and the cellular membrane compartments and their role at distinct stages of the cycle also remain to be finely characterized. Here again, understanding those processes may contribute to the development of novel antiviral strategies.

However, it is very likely that the most significant impact of the discovery of the liquid nature of viral factories will be in the area of innate immunity. Indeed, the liquid nature of viral factories as well as the increasing number of innate immunity actors that have been demonstrated to form biomolecular condensates, invite us to revisit the interactions between the viral infection and the cellular defenses. This interplay is certainly much more subtle than currently thought. Therefore, we look forward to an integrated vision of the interactions between viruses and innate immunity that takes into account all the novel data of this booming field. [17] D. Kolakofsky, Paramyxovirus RNA synthesis, mRNA editing, and genome hexamer phase: A review, Virology, 498 (2016) 94-98.

[18] Negri, A, Contributo allo studio dell'eziologia della rabbia, Boll Soc Med-Chir Pavia, (1903) 1459-1460. [151] . a number of Asp residues and number of Glu residues. Frequency of negatively charged residues. b number of Lys residues and number of Arg residues. Frequency of positively charged residues. c Net charge per residue = (number of Arg residues + number of Lys residuesnumber of Asp residuesnumber of Glu residues) / total number of residues in the sequence d number of Phe residues, number of Tyr residues and number of Trp residues. Frequency of aromatic residues. 2 for HSV-1, a model of VRC formation that is not based on liquid-liquid phase separation has been proposed [69] . NTD stands for N-terminal domain CTD and CTD for C-terminal domain.

Left part: Space-filling model of VSV N-RNA complex (X-Ray structure of a 10 N subunit ring (in shades of purple) associated with 90 RNA bases (in red) (2GIC.pdb) [158] . Each VSV N subunit interacts with 9 RNA bases. In this conformation, the RNA molecule is clamped at the interface of the NTD and the CTD. Each N subunit is shown in a different color indicating that the NTD arm from the n th subunit reaches over to the (n-1) th sub-unit and its CTD arm reaches over to the (n+1) th sub-unit. This arrangement leads to the interaction of both (n+1) th

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Actin-Modulating Protein Cofilin Is Involved in the Formation of Measles Virus Ribonucleoprotein Complex at the Perinuclear Region

p38 and OGT sequestration into viral inclusion bodies in cells infected with human respiratory syncytial virus suppresses MK2 activities and stress granule assembly

The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression

Host factor SMYD3 is recruited by Ebola virus nucleoprotein to facilitate viral mRNA transcription

The Cellular Protein CAD is Recruited into Ebola Virus Inclusion Bodies by the Nucleoprotein NP to Facilitate Genome Replication and Transcription

Cytoplasmic Relocalization and Colocalization with Viroplasms of Host Cell Proteins, and Their Role in Rotavirus Infection

Proteomics of Herpes Simplex Virus Replication Compartments: Association of Cellular DNA Replication, Repair, Recombination, and Chromatin Remodeling Proteinswith ICP8

Further Studies on the Replication of Rabies and Rabies-Like Viruses in Organized Cultures of Mammalian Neural Tissues

Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles

Interplay between innate immunity and negative-strand RNA viruses: towards a rational model

Rabies Viral Mechanisms to Escape the IFN System: The Viral Protein P Interferes with IRF-3, Stat1, and PML Nuclear Bodies

Identification of the Rabies Virus Alpha/Beta Interferon Antagonist: Phosphoprotein P Interferes with Phosphorylation of Interferon Regulatory Factor 3

The Nucleocytoplasmic Rabies Virus P Protein Counteracts Interferon Signaling by Inhibiting both Nuclear Accumulation and DNA Binding of STAT1

Rabies Virus P Protein Interacts with STAT1 and Inhibits Interferon Signal Transduction Pathways

Ebola Virus VP35 Protein Binds Double-Stranded RNA and Inhibits Alpha/Beta Interferon Production Induced by RIG-I Signaling

Structural basis for Marburg virus VP35-mediated immune evasion mechanisms

Ebola Virus VP35 Antagonizes PKR Activity through Its C-Terminal Interferon Inhibitory Domain

Ebola Virus Protein VP35 Impairs the Function of Interferon Regulatory Factor-Activating Kinases IKKɛ and TBK-1

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

Inducible expression of the P, V, and NP genes of the paramyxovirus simian virus 5 in cell lines and an examination of NP-P and NP-V interactions

Formation of Antiviral Cytoplasmic Granules during Orthopoxvirus Infection

DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation

Critical Role of an Antiviral Stress Granule Containing RIG-I and PKR in Viral Detection and Innate Immunity

MDA5 localizes to stress granules, but this localization is not required for the induction of type I interferon

Induction of Stress Granule-Like Structures in Vesicular Stomatitis Virus-Infected Cells

Mammalian orthoreovirus particles induce and are recruited into stress granules at early times postinfection

Mammalian Orthoreovirus Factories Modulate Stress Granule Protein Localization by Interaction with G3BP1

G3BP1 Is a Tunable Switch that Triggers Phase Separation to Assemble Stress Granules

Rotavirus Induces Formation of Remodeled Stress Granules and P Bodies and Their Sequestration in Viroplasms To Promote Progeny Virus Production

DNA-induced liquid phase condensation of cGAS activates innate immune signaling

PKR-dependent cytosolic cGAS foci are necessary for intracellular DNA sensing

Mx GTPases: dynamin-like antiviral machines of innate immunity

Role of Promyelocytic Leukemia Protein in Host Antiviral Defense

Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression

The Role of Promyelocytic Leukemia Nuclear Bodies During HPV Infection

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

Sp100 Provides Intrinsic Immunity against Human Papillomavirus Infection

Differential Role of Sp100 Isoforms in Interferon-Mediated Repression of Herpes Simplex Virus Type 1

Immediate-Early Protein Expression

Human Cytomegalovirus Infection Causes Degradation of Sp100 Proteins That Suppress Viral Gene Expression

A Viral Ubiquitin Ligase Has Substrate Preferential SUMO Targeted Ubiquitin Ligase Activity that Counteracts Intrinsic Antiviral Defence

The Adenoviral Oncogene E1A-13S Interacts with a Specific Isoform of the Tumor Suppressor PML To Enhance Viral Transcription

Emerging Role of PML Nuclear Bodies in Innate Immune Signaling

Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection

Replication of ICP0-Null Mutant Herpes Simplex Virus Type 1 Is Restricted by both PML and Sp100

Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

Differential suppressive effect of promyelocytic leukemia protein on the replication of different subtypes/strains of influenza A virus

Resistance to Rabies Virus Infection Conferred by the PMLIV Isoform

Implication of PMLIV in Both Intrinsic and Innate Immunity

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

Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules

High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies

Analyzing Protein Disorder with IUPred2A

Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

RSV hijacks cellular protein phosphatase 1 to regulate M2-1 phosphorylation and viral transcription

Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription

The spatio-temporal distribution dynamics of Ebola virus proteins and RNA in infected cells

DNA Virus Replication Compartments

Linkage of Transcription and Translation within Cytoplasmic Poxvirus DNA Factories Provides a Mechanism to Coordinate Viral and Usurp Host Functions

Structure of the Vesicular Stomatitis Virus Nucleoprotein-RNA Complex

Near-atomic cryo-EM structure of the helical measles virus nucleocapsid

Solution Structure of the C-Terminal Nucleoprotein-RNA Binding Domain of the Vesicular Stomatitis Virus Phosphoprotein

Structure of the Tetramerization Domain of Measles Virus Phosphoprotein

Structural basis for the attachment of a paramyxoviral polymerase to its template

This work was supported by the CNRS, the University Paris-Saclay, la Fondation Bettencourt and by the Agence Nationale de la Recherche (ANR-19-CE15-0024-01). QN is a postdoctoral fellow supported by a grant on the ANR contract. 

-ssRNA J o u r n a l P r e -p r o o f