scholarly journals Mechanism of Viral Glycoprotein Targeting by Membrane-Associated RING-CH Proteins

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Cheng Man Lun ◽  
Abdul A. Waheed ◽  
Ahlam Majadly ◽  
Nicole Powell ◽  
Eric O. Freed
Keyword(s):  
Antiviral Activity ◽  
Envelope Glycoproteins ◽  
Type I ◽  
Viral Glycoprotein ◽  
Enveloped Viruses ◽  
S Protein ◽  
Virion Incorporation ◽  
Endogenous Expression ◽  
Viral Glycoproteins ◽  
Hiv 1

ABSTRACT An emerging class of cellular inhibitory proteins has been identified that targets viral glycoproteins. These include the membrane-associated RING-CH (MARCH) family of E3 ubiquitin ligases that, among other functions, downregulate cell surface proteins involved in adaptive immunity. The RING-CH domain of MARCH proteins is thought to function by catalyzing the ubiquitination of the cytoplasmic tails (CTs) of target proteins, leading to their degradation. MARCH proteins have recently been reported to target retroviral envelope glycoproteins (Env) and vesicular stomatitis virus G glycoprotein (VSV-G). However, the mechanism of antiviral activity remains poorly defined. Here we show that MARCH8 antagonizes the full-length forms of HIV-1 Env, VSV-G, Ebola virus glycoprotein (EboV-GP), and the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thereby impairing the infectivity of virions pseudotyped with these viral glycoproteins. This MARCH8-mediated targeting of viral glycoproteins requires the E3 ubiquitin ligase activity of the RING-CH domain. We observe that MARCH8 protein antagonism of VSV-G is CT dependent. In contrast, MARCH8-mediated targeting of HIV-1 Env, EboV-GP, and SARS-CoV-2 S protein by MARCH8 does not require the CT, suggesting a novel mechanism of MARCH-mediated antagonism of these viral glycoproteins. Confocal microscopy data demonstrate that MARCH8 traps the viral glycoproteins in an intracellular compartment. We observe that the endogenous expression of MARCH8 in several relevant human cell types is rapidly inducible by type I interferon. These results help to inform the mechanism by which MARCH proteins exert their antiviral activity and provide insights into the role of cellular inhibitory factors in antagonizing the biogenesis, trafficking, and virion incorporation of viral glycoproteins. IMPORTANCE Viral envelope glycoproteins are an important structural component on the surfaces of enveloped viruses that direct virus binding and entry and also serve as targets for the host adaptive immune response. In this study, we investigate the mechanism of action of the MARCH family of cellular proteins that disrupt the trafficking and virion incorporation of viral glycoproteins across several virus families. This research provides novel insights into how host cell factors antagonize viral replication, perhaps opening new avenues for therapeutic intervention in the replication of a diverse group of highly pathogenic enveloped viruses.

scholarly journals Mechanism of Viral Glycoprotein Targeting by Membrane-associated-RING-CH Proteins

2021 ◽  
Author(s):  
Cheng Man Lun ◽  
Abdul A. Waheed ◽  
Alhlam Majadly ◽  
Nicole Powell ◽  
Eric O. Freed
Keyword(s):  
Antiviral Activity ◽  
Envelope Glycoproteins ◽  
Type I ◽  
Viral Glycoprotein ◽  
Enveloped Viruses ◽  
S Protein ◽  
Virion Incorporation ◽  
Endogenous Expression ◽  
Viral Glycoproteins ◽  
Hiv 1

AbstractAn emerging class of cellular inhibitory proteins has been identified that targets viral glycoproteins. These include the membrane-associated RING-CH (MARCH) family of E3 ubiquitin ligases that, among other functions, downregulate cell-surface proteins involved in adaptive immunity. The RING-CH domain of MARCH proteins is thought to function by catalyzing the ubiquitination of the cytoplasmic tails (CTs) of target proteins, leading to their degradation. MARCH proteins have recently been reported to target retroviral envelope glycoproteins (Env) and vesicular stomatitis virus G glycoprotein (VSV-G). However, the mechanism of antiviral activity remains poorly defined. Here we show that MARCH8 antagonizes the full-length forms of HIV-1 Env, VSV-G, Ebola virus glycoprotein (EboV-GP), and the spike (S) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) thereby impairing the infectivity of virions pseudotyped with these viral glycoproteins. This MARCH8-mediated targeting of viral glycoproteins requires the E3 ubiquitin ligase activity of the RING-CH domain. We observe that MARCH8 protein antagonism of VSV-G is CT dependent. In contrast, MARCH8-mediated targeting of HIV-1 Env, EboV-GP and SARS-CoV-2 S protein by MARCH8 does not require the CT, suggesting a novel mechanism of MARCH-mediated antagonism of these viral glycoproteins. Confocal microscopy data demonstrate that MARCH8 traps the viral glycoproteins in an intracellular compartment. We observe that the endogenous expression of MARCH8 in several relevant human cell types is rapidly inducible by type I interferon. These results help to inform the mechanism by which MARCH proteins exert their antiviral activity and provide insights into the role of cellular inhibitory factors in antagonizing the biogenesis, trafficking, and virion incorporation of viral glycoproteins.ImportanceViral envelope glycoproteins are an important structural component on the surface of enveloped viruses that direct virus binding and entry and also serve as targets for the host adaptive immune response. In this study, we investigate the mechanism of action of the MARCH family of cellular proteins that disrupt the trafficking and virion incorporation of viral glycoproteins across several virus families. This research provides novel insights into how host cell factors antagonize viral replication, perhaps opening new avenues for therapeutic intervention in the replication of a diverse group of highly pathogenic enveloped viruses.

scholarly journals Does the Cytoplasmic Tail Matter? Mechanism of Viral Envelope Glycoprotein Targeting by Membrane-Associated-RING-CH (MARCH) Proteins

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 21
Author(s):  
Cheng man Lun ◽  
Abdul A. Waheed ◽  
Eric O. Freed
Keyword(s):  
Antiviral Activity ◽  
Envelope Glycoprotein ◽  
Protein Targeting ◽  
Viral Envelope ◽  
Surface Proteins ◽  
Type I Interferons ◽  
Type I ◽  
Endogenous Expression ◽  
Viral Glycoproteins ◽  
Hiv 1

The MARCH family of RING-finger E3 ubiquitin ligases comprise 11 members that have been reported to play a variety of roles in the downregulation of cell-surface proteins involved in adaptive immunity. The RING-CH domain of MARCH proteins is thought to ubiquitinate the cytoplasmic tails (CTs) of target proteins, leading to protein degradation through either lysosomal or proteasomal pathways. Three MARCH proteins (MARCH1, 2, and 8) have recently been reported to target the HIV-1 envelope glycoprotein (Env) and vesicular stomatitis virus G glycoprotein (VSV-G), thereby impairing the infectivity of HIV-1 virions bearing HIV-1 Env or VSV-G. However, the mechanism of antiviral activity remains poorly defined. Our data show that MARCH proteins antagonize the full-length forms of HIV-1 Env, VSV-G, and Ebola glycoprotein (GP), and impair the infectivity of HIV-1 virions bearing these viral glycoproteins. This Env-targeting activity of the MARCH proteins requires the E3 ubiquitin ligase activity of the RING-CH domain. We observe that the MARCH protein targeting of VSV-G is, to a large extent, CT-dependent. In striking contrast, the MARCH-protein targeting of HIV-1 Env and Ebola GP does not require the CT. Confocal microscopy data demonstrate that MARCH proteins are able to trap the viral glycoproteins in an intracellular compartment. We observe that the endogenous expression of MARCH8 in T-cell lines and PBMCs is inducible by type I interferons (a and b) and is also upregulated by HIV-1 infection. Current studies are aimed at identifying the cellular target for MARCH-mediated ubiquitination in the context of their antiviral activity. These results will clarify the mechanism by which MARCH proteins antagonize viral glycoproteins and provide insights into the antiviral role of cellular inhibitory factors in Env biogenesis, trafficking, and virion incorporation.

scholarly journals NICTABA and UDA, two GlcNAc-binding lectins with unique antiviral activity profiles

2015 ◽  
Vol 70 (6) ◽  
pp. 1674-1685 ◽  
Author(s):  
Stephanie C. Gordts ◽  
Marleen Renders ◽  
Geoffrey Férir ◽  
Dana Huskens ◽  
Els J. M. Van Damme ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Antiviral Activity ◽  
Influenza A ◽  
Specific Binding ◽  
Tobacco Plant ◽  
Human Monoclonal Antibody ◽  
Envelope Glycoproteins ◽  
Carbohydrate Binding ◽  
Enveloped Viruses ◽  
Hiv 1

Abstract Objectives This study aimed to assess the antiviral properties of a unique lectin (NICTABA) produced by the tobacco plant, Nicotiana tabacum. Methods Cellular assays were used to investigate the antiviral activity of NICTABA and Urtica dioica agglutinin (UDA). Surface plasmon resonance (SPR) studies were performed to study the sugar specificity and the interactions of both lectins with the envelope glycoproteins of HIV-1. Results The N-acetyl-d-glucosamine (GlcNAc)-binding lectins exhibited broad-spectrum activity against several families of enveloped viruses including influenza A/B, Dengue virus type 2, herpes simplex virus types 1 and 2 and HIV-1/2. The IC50 of NICTABA for various HIV-1 strains, clinical isolates and HIV-2 assessed in PBMCs ranged from 5 to 30 nM. Furthermore, NICTABA inhibited syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T lymphocytes and prevented DC-SIGN-mediated HIV-1 transmission to CD4+ target T lymphocytes. However, unlike many other antiviral carbohydrate-binding agents (CBAs) described so far, NICTABA did not block HIV-1 capture to DC-SIGN+ cells and it did not interfere with the binding of the human monoclonal antibody 2G12 to gp120. SPR studies with HIV-1 envelope glycoproteins showed that the affinity of NICTABA for gp120 and gp41 was in the low nanomolar range. The specific binding of NICTABA to gp120 could be prevented in the presence of a GlcNAc trimer, but not in the presence of mannose trimers. NICTABA displayed no antiviral activity against non-enveloped viruses. Conclusions Since CBAs possess a high genetic barrier for the development of viral resistance and NICTABA shows a broad antiviral activity profile, this CBA may qualify as a potential antiviral candidate with a pleiotropic mode of action aimed at targeting the entry of enveloped viruses.

scholarly journals Exocytosis of Alphaherpesvirus Virions, Light Particles, and Glycoproteins Uses Constitutive Secretory Mechanisms

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Ian B. Hogue ◽  
Julian Scherer ◽  
Lynn W. Enquist
Keyword(s):  
Plasma Membrane ◽  
Virus Particle ◽  
Immune Evasion ◽  
Host Cells ◽  
Type I ◽  
Rab Gtpases ◽  
Viral Glycoprotein ◽  
Particle Assembly ◽  
Viral Glycoproteins ◽  
Light Particles

ABSTRACTMany molecular and cell biological details of the alphaherpesvirus assembly and egress pathway remain unclear. Recently we developed a live-cell fluorescence microscopy assay of pseudorabies virus (PRV) exocytosis, based ontotalinternalreflectionfluorescence (TIRF) microscopy and a virus-encoded pH-sensitive fluorescent probe. Here, we use this assay to distinguish three classes of viral exocytosis in a nonpolarized cell type: (i) trafficking of viral glycoproteins to the plasma membrane, (ii) exocytosis of viral light particles, and (iii) exocytosis of virions. We find that viral glycoproteins traffic to the cell surface in association with constitutive secretory Rab GTPases and exhibit free diffusion into the plasma membrane after exocytosis. Similarly, both virions and light particles use these same constitutive secretory mechanisms for egress from infected cells. Furthermore, we show that viral light particles are distinct from cellular exosomes. Together, these observations shed light on viral glycoprotein trafficking steps that precede virus particle assembly and reinforce the idea that virions and light particles share a biogenesis and trafficking pathway.IMPORTANCEThe alphaherpesviruses, including the important human pathogens herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV), are among the few viruses that have evolved to exploit the mammalian nervous system. These viruses typically cause mild recurrent herpetic or zosteriform lesions but can also cause debilitating herpes encephalitis, more frequently in very young, old, immunocompromised, or nonnatural hosts. Importantly, many of the molecular and cellular mechanisms of viral assembly and egress remain unclear. This study addresses the trafficking of viral glycoproteins to the plasma membrane, exocytosis of light particles, and exocytosis of virions. Trafficking of glycoproteins affects immune evasion and pathogenesis and may precede virus particle assembly. The release of light particles may also contribute to immune evasion and pathogenesis. Finally, exocytosis of virions is important to understand, as this final step in the virus replication cycle produces infectious extracellular particles capable of spreading to the next round of host cells.

scholarly journals Rapid Prescreening for Antiviral Agents against HIV-1 Based on Their Inhibitory Activity in Site-Directed Immunoassays. Approaches Applicable to Epidemic HIV-1 Strains

1993 ◽  
Vol 4 (4) ◽  
pp. 207-214 ◽  
Author(s):  
A. R. Neurath ◽  
N. Strick ◽  
S. Jiang
Keyword(s):  
Antiviral Activity ◽  
North American ◽  
Antiviral Agents ◽  
Envelope Glycoproteins ◽  
V3 Loop ◽  
European North ◽  
Consensus Peptide ◽  
Antiviral Chemotherapy ◽  
Anti Hiv ◽  
Hiv 1

Several compounds, including the triphenylmethane derivative aurintricarboxylic acid (ATA) and porphyrins, were reported to inhibit the binding of anti-V3 loop-specific antibodies to the V3 loop of gp120 from HIV-1 III-B and to have antiviral activity, probably due to interference with the biological function of the V3 loop. However, these compounds can be applied to antiviral chemotherapy only if they interact with envelope glycoproteins from a multitude of epidemic HIV-1 strains and inhibit their replication. Since recombinant envelope glycoproteins, synthetic peptides and anti-V3 monoclonal antibodies may not be available for these HIV-1 strains, alternative assays are needed to prescreen different compounds for potential antiviral activity against these viruses. Results presented here indicate that: (1) virions of HIV-1 MN, most closely related to primary HIV-1 isolates from European and North American countries, and human anti-HIV-1 antibodies, can also be used for rapid prescreening of antiviral agents, (2) compounds with antiviral activity against HIV-1 MN, discerned by site-directed immunoassays, inhibited the reaction of human anti-HIV-1 with a V3 loop consensus peptide corresponding to European/North American HIV-1 isolates, and (3) meso-tetra (4-carboxyphenyl) porphine (MTCPP), one of the most potent inhibitors of HIV-1 replication selected on the basis of site-directed immunoassays, preferentially attached to the V3 loop of gp120.

scholarly journals Activity of and Effect of Subcutaneous Treatment with the Broad-Spectrum Antiviral Lectin Griffithsin in Two Laboratory Rodent Models

2013 ◽  
Vol 58 (1) ◽  
pp. 120-127 ◽  
Author(s):  
Christopher Barton ◽  
J. Calvin Kouokam ◽  
Amanda B. Lasnik ◽  
Oded Foreman ◽  
Alexander Cambon ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Ebola Virus ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Enveloped Viruses ◽  
Minimal Toxicity ◽  
Human T Cell ◽  
Long Term Treatment ◽  
Hiv 1

ABSTRACTGriffithsin (GRFT) is a red-alga-derived lectin that binds the terminal mannose residues of N-linked glycans found on the surface of human immunodeficiency virus type 1 (HIV-1), HIV-2, and other enveloped viruses, including hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus (SARS-CoV), and Ebola virus. GRFT displays no human T-cell mitogenic activity and does not induce production of proinflammatory cytokines in treated human cell lines. However, despite the growing evidence showing the broad-spectrum nanomolar or better antiviral activity of GRFT, no study has reported a comprehensive assessment of GRFT safety as a potential systemic antiviral treatment. The results presented in this work show that minimal toxicity was induced by a range of single and repeated daily subcutaneous doses of GRFT in two rodent species, although we noted treatment-associated increases in spleen and liver mass suggestive of an antidrug immune response. The drug is systemically distributed, accumulating to high levels in the serum and plasma after subcutaneous delivery. Further, we showed that serum from GRFT-treated animals retained antiviral activity against HIV-1-enveloped pseudoviruses in a cell-based neutralization assay. Overall, our data presented here show that GRFT accumulates to relevant therapeutic concentrations which are tolerated with minimal toxicity. These studies support further development of GRFT as a systemic antiviral therapeutic agent against enveloped viruses, although deimmunizing the molecule may be necessary if it is to be used in long-term treatment of chronic viral infections.

scholarly journals MARCH8 inhibits viral infection by two different mechanisms

2020 ◽  
Author(s):  
Yanzhao Zhang ◽  
Takuya Tada ◽  
Seiya Ozono ◽  
Satoshi Kishigami ◽  
Hideaki Fujita ◽  
...  
Keyword(s):  
Viral Infection ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Envelope Glycoproteins ◽  
Intracellular Protein ◽  
Virion Incorporation ◽  
Lysine Residues ◽  
Vesicular Stomatitis ◽  
Dependent Pathway ◽  
Hiv 1

ABSTRACTMembrane-associated RING-CH 8 (MARCH8) inhibits infection with both HIV-1 and vesicular stomatitis virus G-glycoprotein (VSV-G)-pseudotyped viruses by reducing virion incorporation of envelope glycoproteins. The molecular mechanisms by which MARCH8 targets envelope glycoproteins remain unknown. Here, we show two different mechanisms by which MARCH8 inhibits viral infection. Viruses pseudotyped with the VSV-G mutant, in which cytoplasmic lysine residues were mutated, were insensitive to the inhibitory effect of MARCH8, whereas those with a similar lysine mutant of HIV-1 Env remained sensitive to it. Indeed, the wild-type VSV-G, but not its lysine mutant, was ubiquitinated by MARCH8. Furthermore, the MARCH8 mutant, which had a disrupted cytoplasmic tyrosine motif that is critical for intracellular protein sorting, did not inhibit HIV-1 Env-mediated infection, while it still impaired infection by VSV-G-pseudotyped viruses. Overall, we conclude that MARCH8 reduces viral infectivity by downregulating envelope glycoproteins through two different mechanisms mediated by a ubiquitination-dependent or tyrosine motif-dependent pathway.

scholarly journals Mechanism of the Antiviral Activity of New Aurintricarboxylic Acid Analogues

1996 ◽  
Vol 7 (3) ◽  
pp. 142-152 ◽  
Author(s):  
D. Reymen ◽  
M. Witvrouw ◽  
J. A. Esté ◽  
J. Neyts ◽  
D. Schols ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Parent Compound ◽  
Flow Cytometric Analysis ◽  
Human Herpesvirus ◽  
Enveloped Viruses ◽  
Herpesvirus Type ◽  
Aurintricarboxylic Acid ◽  
Dna And Rna ◽  
Human Herpesvirus Type ◽  
Hiv 1

Various new aurintricarboxylic acid (ATA) polymer analogues have been evaluated for their antiviral activity against a wide array of DNA and RNA viruses, and their mechanism of action against human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1). Most of the polymers exhibited marked antiviral activity against a variety of enveloped viruses, but not against non-enveloped viruses. The ATA polymers displayed the most pronounced activity against HIV-1, HCMV and human herpesvirus type 6 (HHV-6). Their action against HCMV and HIV could be ascribed to inhibition of the initial attachment of virus particles to the cells. Using radiolabelled virus, we proved that the polymers inhibit the binding of HCMV to HEL fibroblasts. By flow cytometric analysis, we demonstrated that these new polymers interfere with (i) the binding of OKT4A monoclonal antibody (mAb) to the cellular CD4 receptor, (ii) the binding of anti-gp120 mAb to HIV-1 glycoprotein (gp) 120, and (iii) the adsorption of HIV-1 virions and recombinant HIV-1gp120 (rgp120) to MT-4 cells. The presence of a salicylic acid substituent on the central bridging carbon in the parent compound ATA seems to play an important role in the anti-HIV activity of these ATA related polymer analogues.

scholarly journals Effect of HIV-1 Env on SERINC5 Antagonism

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Saina Beitari ◽  
Shilei Ding ◽  
Qinghua Pan ◽  
Andrés Finzi ◽  
Chen Liang
Keyword(s):  
Antiviral Activity ◽  
High Frequency ◽  
Neutralizing Antibodies ◽  
Broadly Neutralizing Antibodies ◽  
Viral Loads ◽  
Virion Incorporation ◽  
Viral Particles ◽  
Ccr5 Inhibitor ◽  
Hiv 1

ABSTRACT SERINC5 is able to restrict HIV-1 infection by drastically impairing the infectivity of viral particles. Studies have shown that the HIV-1 Nef protein counters SERINC5 through downregulating SERINC5 from the cell surface and preventing the virion incorporation of SERINC5. In addition, the Env proteins of some HIV-1 strains can also overcome SERINC5 inhibition. However, it is unclear how HIV-1 Env does so and why HIV-1 has two mechanisms to resist SERINC5 inhibition. The results of this study show that neither Env nor Nef prevents high levels of ectopic SERINC5 from being incorporated into HIV-1 particles, except that Env, but not Nef, is able to resist inhibition by virion-associated SERINC5. Testing of a panel of HIV-1 Env proteins from different subtypes revealed a high frequency of SERINC5-resistant Envs. Interestingly, although the SERINC5-bearing viruses were not inhibited by SERINC5 itself, they became more sensitive to the CCR5 inhibitor maraviroc and some neutralizing antibodies than the SERINC5-free viruses, which suggests a possible influence of SERINC5 on Env function. We conclude that HIV-1 Env is able to overcome SERINC5 without preventing SERINC5 virion incorporation. IMPORTANCE HIV-1 Nef is known to enhance the infectivity of HIV-1 particles and to contribute to the maintenance of high viral loads in patients. However, the underlying molecular mechanism remained elusive until the recent discovery of the antiviral activity of SERINC5. SERINC5 profoundly inhibits HIV-1 but is antagonized by Nef, which prevents the incorporation of SERINC5 into viral particles. Here, we show that HIV-1 Env, but not Nef, is able to resist high levels of SERINC5 without excluding SERINC5 from incorporation into viral particles. However, the virion-associated SERINC5 renders HIV-1 more sensitive to some broadly neutralizing antibodies. It is possible that, under the pressure of some neutralizing antibodies in vivo, HIV-1 needs Nef to remove SERINC5 from viral particles, even though viral Env is able to resist virion-associated SERINC5.

scholarly journals SERINC Proteins Potentiate Antiviral Type I IFN Induction and Proinflammatory Signaling Pathways

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 51
Author(s):  
Cong Zeng ◽  
Abdul A. Waheed ◽  
Tianliang Li ◽  
Jingyou Yu ◽  
Yi-Min Zheng ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Signaling Pathways ◽  
Ebola Virus ◽  
Type I ◽  
Restriction Factors ◽  
Asian Strain ◽  
Immunodeficiency Virus ◽  
Vesicular Stomatitis ◽  
Mitochondrial Antiviral Signaling ◽  
Hiv 1

T cell SERINC proteins were recently identified as human immunodeficiency virus (HIV) restriction factors that diminish viral infectivity by incorporation into virions. Here we provide evidence that SERINC3 and SERINC5 perform additional antiviral activity by enhancing the type I interferon (IFN-I) and NF-κB signaling pathways. SERINC5 interacts with the mitochondrial antiviral-signaling (MAVS) and TRAF6 proteins, resulting in MAVS aggregation and TRAF6 polyubiquitination. Knockdown of SERINC5 in the target cell increases single-round HIV-1 infectivity, as well as infection by recombinant vesicular stomatitis virus (rVSV) bearing VSV-G or Ebola virus (EBOV) glycoprotein (GP). Infection by an endemic Asian strain of Zika virus (ZIKV) FSS13025 is also enhanced by SERINC5 knockdown, suggesting that SERINC5 has direct antiviral activity. Further experiments indicated that the antiviral activity of SERINC5 is IFN-I dependent. Altogether, our work uncovered a new function of SERINC proteins that promotes IFN-I and NF-B inflammatory signaling, thus contributing to SERINC-mediated antiviral activity.

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