# bib

id: cord-341513-e6p3lrlf
author: Li, Yunchuan
date: 2017-09-29
txt: ./txt/cord-341513-e6p3lrlf.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/29033949/
doi: 10.3389/fimmu.2017.01237
summary:
  title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection To determine the role of lncRNAs in inflammatory cytokine production, the cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. To examine the role of lncRNA E52329 and N54010 in regulating the kinase activity of MKK4/JNK pathway, BV2 cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. The results of our study reveal the first experimental evidence demonstrating the complex regulation of lncRNAs by JEV infection in mice brain and microglial cells. Third, the integration of microarray platform, quantitative real-time PCR, GO analysis, pathways analysis, and lncRNA-mRNA coexpression network analysis has allowed us to conduct an active comparative genomics and bioinformatics study to reveal host lncRNAs expression patterns associated with JEV infection.

title:
  Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection

abstract:
  Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. JEV-induced neuroinflammation is characterized by profound neuronal cells damage accompanied by activation of glial cells. Albeit long non-coding RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound effects on various biological processes, it is unknown how lncRNAs regulate JEV-induced inflammation. Here, using microarray approach, we identified 618 lncRNAs and 1,007 mRNAs differentially expressed in JEV-infected mice brain. The functional annotation analysis revealed that differentially regulated transcripts were predominantly involved in various signaling pathways related to host immune and inflammatory responses. The lncRNAs with their potential to regulate JEV-induced inflammatory response were identified by constructing the lncRNA-mRNA coexpression network. Furthermore, silencing of the two selected lncRNAs (E52329 and N54010) resulted in reducing the phosphorylation of JNK and MKK4, which are known to be involved during inflammatory response. Collectively, we first demonstrated the transcriptomic landscape of lncRNAs in mice brain infected with JEV and analyzed the coexpression network of differentially regulated lncRNAs and mRNAs during JEV infection. Our results provide a better understanding of the host response to JEV infection and suggest that the identified lncRNAs may be used as potential therapeutic targets for the management of Japanese encephalitis.


id: cord-342776-hkjhqgie
author: Jewett, Anahid
date: 2020-07-10
txt: ./txt/cord-342776-hkjhqgie.txt
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url: https://doi.org/10.3389/fimmu.2020.01692
doi: 10.3389/fimmu.2020.01692
summary:
  While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease. In particular, in the peripheral blood of patients that were infected with SARS, it was noted that there were significantly lower numbers of natural killer (NK) cells compared to healthy subjects (14) . As mentioned above the infectious agent of COVID-19 disease depletes NK cells in the peripheral blood, and potentially even in the lung tissues of patients, thereby, disabling and depleting the core immune effectors necessary to remove the virus and regulate uncontrolled immune activation.

title:
  The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions

abstract:
  Coronavirus-induced disease-2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. This commentary outlines what is the reported literature thus far on the effect of virus on NK cells known to kill virally infected cells. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease.


id: cord-343824-00mqmpzw
author: Qian, Wei
date: 2017-07-03
url: https://www.ncbi.nlm.nih.gov/pubmed/28717359/
doi: 10.3389/fimmu.2017.00779
title:
  The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3

abstract:
  Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity.


id: cord-344093-3bniy5b5
author: Peteranderl, Christin
date: 2017-03-22
txt: ./txt/cord-344093-3bniy5b5.txt
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url: https://doi.org/10.3389/fimmu.2017.00313
doi: 10.3389/fimmu.2017.00313
summary:
  A prominent regulator of disease outcome, especially in-but not limited to-respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. (73) Cell death induction, e.g., Bcl-2-associated X protein, caspase-8, Fas-associated protein with death domain, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL) dsRNA, polyI:C (4, 110) IAV (4, 5, 10, 115) Sendai virus (110) TRAIL Virus control by apoptosis induction in infected cells IAV (6, 170, 171) Tissue injury by apoptosis of both infected and non-infected alveolar epithelial cells, lung macrophages IAV (5, 7, 10) RSV (137) Necrosis of fibroblasts, dendritic cells, and epithelial cells IAV (146, 147, 168) Increased cellular infiltration CoV (175) Decreased expression of Na,K-ATPase, impaired epithelial fluid reabsorption IAV (11) iNTRODUCTiON In 1957, Isaacs and Lindenmann (1) first recognized the potential of a soluble and probably cell-derived factor to combat influenza virus infection and named this factor interferon [(IFN) from latin interferre, to interfere].

title:
  The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond

abstract:
  Interferons (IFNs) are well described to be rapidly induced upon pathogen-associated pattern recognition. After binding to their respective IFN receptors and activation of the cellular JAK/signal transducer and activator of transcription signaling cascade, they stimulate the transcription of a plethora of IFN-stimulated genes (ISGs) in infected as well as bystander cells such as the non-infected epithelium and cells of the immune system. ISGs may directly act on the invading pathogen or can either positively or negatively regulate the innate and adaptive immune response. However, IFNs and ISGs do not only play a key role in the limitation of pathogen spread but have also been recently found to provoke an unbalanced, overshooting inflammatory response causing tissue injury and hampering repair processes. A prominent regulator of disease outcome, especially in—but not limited to—respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. First described as an apoptosis-inducing agent in transformed cells, it is now also well established to rapidly evoke cellular stress pathways in epithelial cells, finally leading to caspase-dependent or -independent cell death. Hereby, pathogen spread is limited; however in some cases, also the surrounding tissue is severely harmed, thus augmenting disease severity. Interestingly, the lack of a strictly controlled and well balanced IFN/TRAIL signaling response has not only been implicated in viral infection but might furthermore be an important determinant of disease progression in bacterial superinfections and in chronic respiratory illness. Conclusively, the IFN/TRAIL signaling axis is subjected to a complex modulation and might be exploited for the evaluation of new therapeutic concepts aiming at attenuation of tissue injury.


id: cord-344610-mqq6fmsp
author: Waumans, Yannick
date: 2015-08-07
txt: ./txt/cord-344610-mqq6fmsp.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/26300881/
doi: 10.3389/fimmu.2015.00387
summary:
  Usually only four prolyl-specific peptidases are considered: DPPIV (EC 3.4.14.5), fibroblast activation protein α (FAP; EC 3.4.21.B28), and the more recently discovered DPP8 and DPP9 (EC 3.4.14). However, due to similarities in substrate specificity and structural homology, it is more relevant to consider a broader family that also includes prolyl oligopeptidase (PREP; EC 3.4.21.26), dipeptidyl peptidase II (DPPII) (EC 3.4.14.2), and prolyl carboxypeptidase (PRCP; EC 3.4.16.2). Three other studies also found no to low DPPIV expression or activity associated with human monocytes and/or macrophages (82, [136] [137] [138] . Dipeptidyl peptidase 4 is present in low amounts on freshly isolated human NK cells and its expression is only upregulated in a small subpopulation after IL-2 stimulation (158) . Dipeptidyl peptidase 8 and 9 have been found to be abundantly present in the macrophage-rich regions of human atherosclerotic plaques and considering DPP9''s role in macrophage activation, it might potentially be involved in atherogenesis (82). Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells

title:
  The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis

abstract:
  Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease.


id: cord-344829-adlp2rjy
title: The Inflammasome in Times of COVID-19
author: de Rivero Vaccari, Juan Carlos
date: 2020-10-08
txt: ./txt/cord-344829-adlp2rjy.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/33149733/
doi: 10.3389/fimmu.2020.583373
summary:
  Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients. Here we review the literature on the role of the inflammasome in CoV infections, which includes how CoVs activate inflammasomes upon infection, the role of the inflammasome in acute respiratory distress syndrome (ARDS), how ventilator-induced lung injury (VILI) activates the inflammasome, how the inflammasome plays a role in the systemic complications associated with COVID-19, and how the inflammasome is involved in the process of Disseminated Intravascular Coagulation (DIC).

abstract:
  Coronaviruses (CoVs) are members of the genus Betacoronavirus and the Coronaviridiae family responsible for infections such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and more recently, coronavirus disease-2019 (COVID-19). CoV infections present mainly as respiratory infections that lead to acute respiratory distress syndrome (ARDS). However, CoVs, such as COVID-19, also present as a hyperactivation of the inflammatory response that results in increased production of inflammatory cytokines such as interleukin (IL)-1β and its downstream molecule IL-6. The inflammasome is a multiprotein complex involved in the activation of caspase-1 that leads to the activation of IL-1β in a variety of diseases and infections such as CoV infection and in different tissues such as lungs, brain, intestines and kidneys, all of which have been shown to be affected in COVID-19 patients. Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients.


id: cord-346389-gbmnoo84
title: The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19
author: Callender, Lauren A.
date: 2020-08-11
url: https://www.ncbi.nlm.nih.gov/pubmed/32903476/
doi: 10.3389/fimmu.2020.01991
abstract:
  Evidence from the global outbreak of SARS-CoV-2 has clearly demonstrated that individuals with pre-existing comorbidities are at a much greater risk of dying from COVID-19. This is of great concern for individuals living with these conditions, and a major challenge for global healthcare systems and biomedical research. Not all comorbidities confer the same risk, however, many affect the function of the immune system, which in turn directly impacts the response to COVID-19. Furthermore, the myriad of drugs prescribed for these comorbidities can also influence the progression of COVID-19 and limit additional treatment options available for COVID-19. Here, we review immune dysfunction in response to SARS-CoV-2 infection and the impact of pre-existing comorbidities on the development of COVID-19. We explore how underlying disease etiologies and common therapies used to treat these conditions exacerbate COVID-19 progression. Moreover, we discuss the long-term challenges associated with the use of both novel and repurposed therapies for the treatment of COVID-19 in patients with pre-existing comorbidities.


id: cord-348283-7xorq5ce
author: Naz, Anam
date: 2020-07-10
txt: ./txt/cord-348283-7xorq5ce.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32754160/
doi: 10.3389/fimmu.2020.01663
summary:
  The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Designed vaccines were then tested with different epitopes, including Truncated Ov-ASP-1 Protein (residues 10-153) and Beta defensin (45 residues long), and constructs having higher antigenicity and that are predicted to produce high antibody titers were added with the multi epitope vaccine construct to the enhance immune response (30) . For the interaction analysis of vaccine 3 and BCR (CD79), the HADDOCK server clustered 140 probable structures into 13 different clusters, which represented a total of 70% of the water-refined models.

title:
  Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach

abstract:
  A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4.


id: cord-350041-b1vmnwv2
author: Cena, Hellas
date: 2020-05-07
txt: ./txt/cord-350041-b1vmnwv2.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32574257/
doi: 10.3389/fimmu.2020.00944
summary:
  There has been a gradual increase in studies exploring prevention and control measures, and we recommend paying close attention to nutrition, which may contribute to modulating some important consequences of COVID-19 infection, as such pro-inflammatory cytokine storm. Unfortunately, we do not yet have weight, height, and waist circumference data for all patients with laboratory-confirmed COVID-19, and, therefore, we cannot disentangle the effects of adiposity on lung function and immune response to viral infection. Recent data on patients with laboratory-confirmed COVID-19 treated at an academic health institution in New York City, the epicenter of the COVID-19 outbreak in the United States, between March 1, 2020, and April 2, 2020, with follow up through April 7, 2020 (13, 14) showed that obesity, after age, was linked to more severe coronavirus cases, with a substantially higher odds ratio than any cardiovascular or pulmonary disease.

title:
  Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection?

abstract:
  Novel coronavirus disease (COVID-19) was declared a global pandemic on March 11, 2020. The outbreak first occurred in Wuhan, Hubei, China, in December 2019 and hit Italy heavily in February 2020. Several countries are adopting complete or partial lockdown to contain the growth of COVID-19 infection. These measures may affect people's mental health and well-being but are necessary to avoid spreading the pandemic. There has been a gradual increase in studies exploring prevention and control measures, and we recommend paying close attention to nutrition, which may contribute to modulating some important consequences of COVID-19 infection, as such pro-inflammatory cytokine storm.


id: cord-350492-1s6wtj25
author: Ruscitti, Piero
date: 2020-05-28
txt: ./txt/cord-350492-1s6wtj25.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32574264/
doi: 10.3389/fimmu.2020.01130
summary:
  On these bases, we aimed to review the similarities between severe COVID-19 and diseases included in hyperferritinemic syndrome, from a pathogenic, clinical, and therapeutic point of view, thus proposing new insights to improve the management of those patients. In addition, it has been shown that increased amounts of pro-inflammatory cytokines, including IL-1β, IL-6, IL-12, IFN-γ, IP-10, and MCP1, were associated with pulmonary inflammation and extensive lung damage in SARS patients (25) , thus suggesting a further pathogenic loop in inducing the cytokine storm. The final result is the uncontrolled proliferation of activated immune cells, the massive production of pro-inflammatory mediators, and the development of cytokine storm syndrome, either in severe COVID-19 or SJIA. Considering the lack of efficacy of antiviral therapy for severe coronavirus infection, it is reasonable to postulate the clinical usefulness of specific immunomodulatory therapies (Figure 1) , as observed for other diseases included in hyperferritinemic syndrome such as intravenous immunoglobulins (IVIGs) and tocilizumab, the humanized monoclonal antibody against IL-6 receptor (7).

title:
  Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm

abstract:
  The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the “hyperferritinemic syndrome” category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies.


id: cord-350836-1enteev7
title: Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5
author: Brisse, Morgan
date: 2019-07-17
url: https://doi.org/10.3389/fimmu.2019.01586
doi: 10.3389/fimmu.2019.01586
abstract:
  RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral double-stranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection. While RIG-I and MDA5 share many genetic, structural and functional similarities, there is increasing evidence that they can have significantly different strategies to recognize different pathogens, PAMPs, and in different host species. This review article discusses the similarities and differences between RIG-I and MDA5 from multiple perspectives, including their structures, evolution and functional relationships with other cellular proteins, their differential mechanisms of distinguishing between host and viral dsRNAs and interactions with host and viral protein factors, and their immunogenic signaling. A comprehensive comparative analysis can help inform future studies of RIG-I and MDA5 in order to fully understand their functions in order to optimize potential therapeutic approaches targeting them.


id: cord-351305-6vtv2xuh
author: Schramm, Markus A.
date: 2020-08-28
txt: ./txt/cord-351305-6vtv2xuh.txt
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url: https://www.ncbi.nlm.nih.gov/pubmed/32983161/
doi: 10.3389/fimmu.2020.02086
summary:
  The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA). Thus, due to severity and refractory disease the previously healthy patient was continuously hospitalized from January to March 2020, receiving intravenous cyclophosphamide (CYCLOPS-protocol, cumulative dose 4.76 g), rituximab (4 × 375 mg/m 2 ), and a long-term, slowly tapered high-dose prednisolone treatment (up to 1 g/day). Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients

title:
  COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis

abstract:
  Immunosuppressive therapies increase the susceptibility of patients to infections. The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA).


id: cord-351431-xcqz9d3t
title: Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19
author: Wang, Jun
date: 2020-08-18
txt: ./txt/cord-351431-xcqz9d3t.txt
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extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.02063
doi: 10.3389/fimmu.2020.02063
summary:
  Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Principal component analysis was performed with R package "FactoMineR" to identify those clinical parameters that contribute most to distinguishing severe, moderate, and mild cases of COVID-19 (28) . For BALF, the most upregulated marker genes were similarly enriched in neutrophils, but more up-regulated genes in monocytes and B cells were observed in COVID-19 patients compared to healthy controls, which is different from the lung samples. Transcriptome analysis of lung specimens and BALF from COVID-19 patients also indicated the most up-regulated marker genes were neutrophil related. Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19

abstract:
  Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7–19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia.


id: cord-352150-ey9kc7zj
author: Degauque, Nicolas
date: 2016-03-24
url: https://doi.org/10.3389/fimmu.2016.00089
doi: 10.3389/fimmu.2016.00089
title:
  Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation

abstract:
  Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed.


id: cord-352230-8mazd3eu
title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status
author: Beeraka, Narasimha M.
date: 2020-09-18
url: https://doi.org/10.3389/fimmu.2020.552925
doi: 10.3389/fimmu.2020.552925
abstract:
  Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs.


id: cord-352737-3ttrx3lf
author: Cunha, Lucas Leite
date: 2020-08-07
txt: ./txt/cord-352737-3ttrx3lf.txt
cache: ./cache/cord-352737-3ttrx3lf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32849623/
doi: 10.3389/fimmu.2020.01748
summary:
  Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Interestingly, polymorphonuclear leucocytes from the elderly are less capable of modulating the triggering receptor expressed on myeloid cell-1 (TREM-1)-induced oxidative bursts, suggesting that TREM-1 signal transduction altered with aging may be one of the mediators of the decrease in microbicidal potential of innate immune cells in older adults (41) .

title:
  Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response

abstract:
  Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.


id: cord-352960-pfccsgco
author: Gössling, Katharina L.
date: 2017-06-30
txt: ./txt/cord-352960-pfccsgco.txt
cache: ./cache/cord-352960-pfccsgco.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2017.00773
doi: 10.3389/fimmu.2017.00773
summary:
  Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous descent diagnosed with ICF syndrome carrying a homozygous missense mutation in the DNMT3B gene (Ala603Thr) with hypogammagobulinemia, normal B cell count, facial anomaly, and failure to thrive. We report the successful allogeneic HSCT of a 1-year-old boy with ICF1 syndrome carrying a homozygous mutation in the DNMT3B gene after receipt of bone marrow cells from the 10/10 HLA-matched clinically healthy sister.

title:
  Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome

abstract:
  Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. He was initially admitted to the hospital with recurrent pulmonary infections from the opportunistic pathogen Pneumocystis jirovecii (PJ). Further immunological workup revealed agammaglobulinemia in the presence of B cells. After successful recovery from the PJ pneumonia, he underwent hematopoietic stem cell transplantation (HSCT) from the HLA-matched healthy sister using a chemotherapeutic conditioning regimen consisting of treosulfan, fludarabine, and thiotepa. Other than acute chemotherapy-associated side effects, no serious adverse events occurred. Six months after HSCT immune-reconstitution, he had a stable chimerism with 2.9% autologous portion in the peripheral blood and a normal differential blood cell count, including all immunoglobulin subtypes. This is one of the first cases of successful HSCT in ICF syndrome. Early diagnosis and subsequent HSCT can prevent severe opportunistic infections and cure the immunodeficiency. Centromeric instability and facial anomaly remain unaffected. Although the long-term patient outcome and the neurological development remain to be seen, this curative therapy for immunodeficiency improves life expectancy and quality of life. This case is meant to raise physicians awareness for ICF syndrome and highlight the consideration for HSCT in ICF syndrome early on.


id: cord-353217-gmc3qrci
title: Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus
author: de Miranda Santos, Isabel Kinney Ferreira
date: 2020-08-04
txt: ./txt/cord-353217-gmc3qrci.txt
cache: ./cache/cord-353217-gmc3qrci.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.01739
doi: 10.3389/fimmu.2020.01739
abstract: nan
summary:
  Recent large observational studies indicate that hydroxychloroquine (HY) does not affect outcomes of patients hospitalized with COVID-19 (1, 2) and may even be harmful (3) . In view of this situation and of the importance of correct interpretation of antibody profiles for planning preventive measures for COVID-19, we would like to bring the attention of readers to studies that raise concerns about the possible impact of HY upon antibody responses to SARS-CoV-2. To the best of our knowledge, there are no new facts in the scientific and medical literature that indicate that the same mechanism could not operate in HY-treated patients suffering from COVID-19 and negatively impact their SARS-CoV-2-specific antibody responses. As more needs to be learned about the role of antibodies in recovery from and protection against infection with SARS-CoV-2, the impact of HY and other treatment regimens on antibody responses requires systematic evaluation.


id: cord-353594-z1vxamvp
author: Gagiannis, Daniel
date: 2020-10-02
txt: ./txt/cord-353594-z1vxamvp.txt
cache: ./cache/cord-353594-z1vxamvp.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.587517
doi: 10.3389/fimmu.2020.587517
summary:
  Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Patients or their relatives had given written informed consent to routine diagnostic procedures (serology, bronchoscopy, radiology) as well as (partial) autopsy in the case of death, respectively, as well as to the scientific use of data and tissue samples in the present study. Our finding that significant ANA titers and/or detection of specific autoantibodies are found in most patients who develop ARDS raises the question if there is a comparable mechanism of lung damage between SARS-CoV-2 infection and exacerbating autoimmune disease. Our observation of CTD-associated autoantibodies together with the CTD-like radiologic and histopathologic lung findings in severe cases of COVID-19 point towards a possible dysregulation of the immune response upon SARS-CoV-2 infection that might fuel organizing pneumonia and trigger interstitial fibrosis, with deleterious effects on the functional outcome in long-term survivors.

title:
  Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD)

abstract:
  BACKGROUND AND OBJECTIVES: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. METHODS: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. RESULTS: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. CONCLUSIONS: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients.


id: cord-353887-f4yd7guj
title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies
author: Tang, Yujun
date: 2020-07-10
url: https://doi.org/10.3389/fimmu.2020.01708
doi: 10.3389/fimmu.2020.01708
abstract:
  Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.


id: cord-354030-8tfg881h
title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches
author: Dong, Rong
date: 2020-07-28
txt: ./txt/cord-354030-8tfg881h.txt
cache: ./cache/cord-354030-8tfg881h.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.01784
doi: 10.3389/fimmu.2020.01784
summary:
  The realm of immunoinformatics tools considers the mechanism of the host immune response to yield additional methodologies in the design of vaccine against diseases are cost-effective and convenient, as in silico predictions can reduce the number of experiments needed (13, 14) . In this present, we employed immunoinformatics to predict multiple immunogenic proteins from the SARS-CoV-2 proteome and thereby design a multi-epitope vaccine. developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . A vaccine based on the spike protein could induce antibodies to block SARS-COV-2 binding and fusion or neutralize virus infection (18) , as well as induce harmful immune responses that cause liver damage (19) . To design an effective vaccine, we selected the SARS-CoV-2 protein through the above-mentioned methods for epitope prediction. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach

abstract:
  COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.


id: cord-354353-hyz0gmpz
author: Farhangrazi, Z. Shadi
date: 2020-09-24
txt: ./txt/cord-354353-hyz0gmpz.txt
cache: ./cache/cord-354353-hyz0gmpz.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3389/fimmu.2020.579352
doi: 10.3389/fimmu.2020.579352
abstract: nan
summary:
  While long-term exposure to air pollutants such as PM 2.5 and nitrous dioxide contributes to persistent inflammatory responses and cardiopulmonary diseases (7) , which might increase vulnerability to COVID-19, it is also plausible that depending on the environment SARS-CoV-2 "hitchhiking" on airborne PM pollutants might be an additional mechanism for spreading the infection. In summary, although long-term exposure to polluted air might increase vulnerability to COVID-19 through prior adverse cellular effects of settled PM (24), our proposed "hitchhiking" hypothesis offers an additional multi-mechanistic pathogenic process through delivery of low viral titres with diverse PM-virus composites and is applicable to both indoor and outdoor situations, where the pathogenic severity is dependent on PM concentration, composition, shape and size as well as the infectious viral load. Contrary to the suggestions that long-term exposure to PM might increase vulnerability to SAR-CoV-2 infection, inhaled PM might promote some forms of immunity to the virus in some individuals.

title:
  Airborne Particulate Matter and SARS-CoV-2 Partnership: Virus Hitchhiking, Stabilization and Immune Cell Targeting — A Hypothesis


id: cord-354620-xf6glr2h
author: Tian, Bin
date: 2020-01-28
url: https://doi.org/10.3389/fimmu.2019.03131
doi: 10.3389/fimmu.2019.03131
title:
  Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus

abstract:
  Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens.


