Inhibition of MAVS Aggregation-Mediated Type-I Interferon Signaling by Foot-and-Mouth Disease Virus VP3

Ekanayaka, Pathum; Lee, Byeong‐Hoon; Weerawardhana, Asela; Chathuranga, Kiramage; Park, Jong Hyeon; Lee, Jong-Soo

doi:10.3390/v13091776

Cited by 10 publications

(6 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria are known to act as an interferon-signalling platform via the MAVS-signalling pathway, and some viral proteins can modulate this mechanism [ 62 , 63 ]. NS1 of IAV appears to block the interaction between RIG-I and MAVS, inhibiting RIG-I-mediated induction of interferon-β [ 64 , 65 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells

Jaafar

Monsion

Mertens

et al. 2023

IJMS

View full text Add to dashboard Cite

Bioinformatic analyses have predicted that orbiviruses encode an additional, small non-structural protein (NS5) from a secondary open reading frame on genome segment 10. However, this protein has not previously been detected in infected mammalian or insect cells. NS5-specific antibodies were generated in mice and were used to identify NS5 synthesised in orbivirus-infected BSR cells or cells transfected with NS5 expression plasmids. Confocal microscopy shows that although NS5 accumulates in the nucleus, particularly in the nucleolus, which becomes disrupted, it also appears in the cell cytoplasm, co-localising with mitochondria. NS5 helps to prevent the degradation of ribosomal RNAs during infection and reduces host-cell protein synthesis However, it helps to extend cell viability by supporting viral protein synthesis and virus replication. Pulldown studies showed that NS5 binds to ssRNAs and supercoiled DNAs and demonstrates interactions with ZBP1, suggesting that it modulates host-cell responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells

Jaafar

Monsion

Mertens

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Therefore, our findings of prM proteins to subvert host innate immunity would contribute to further clarification of the pathogenesis of flaviviruses. In fact, viral structural proteins suppress the IFN-I antiviral response, such as SARS coronaviruses, Foot-andmouth disease virus, Bluetongue virus, and Ebola virus [26,32,[43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling

et al. 2023

View full text Add to dashboard Cite

Background Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive. Results We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus. Conclusion Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

show abstract

“…It is also associated with disruption of RLR-mediated IFN-β signaling by downregulating RIG-I, MDA5 transcript levels ( 52 ), DDX56 dependent inhibition of IRF3 phosphorylation ( 53 ), upregulation of LRRC25 to inhibit G3BP1 mediated RLH signaling pathway ( 9 ). FMDV VP3 mediates the degradation of JAK1 ( 54 ), decreases the expression of RIG-I and MDA5 ( 55 ) and inhibits MAVS aggregation ( 56 ). Furthermore, FMDV VP1 interacts with sorcin to inhibit IFN signaling ( 57 ).…”

Section: Discussionmentioning

confidence: 99%

Foot-and-mouth disease virus non-structural protein 2B downregulates the RLR signaling pathway via degradation of RIG-I and MDA5

Weerawardhana

Uddin²,

Choi³

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Foot-and-mouth disease virus (FMDV) is a single-stranded, positive-sense RNA virus containing at least 13 proteins. Many of these proteins show immune modulation capabilities. As a non-structural protein of the FMDV, 2B is involved in the rearrangement of the host cell membranes and the disruption of the host secretory pathway as a viroporin. Previous studies have also shown that FMDV 2B plays a role in the modulation of host type-I interferon (IFN) responses through the inhibition of expression of RIG-I and MDA5, key cytosolic sensors of the type-I IFN signaling. However, the exact molecular mechanism is poorly understood. Here, we demonstrated that FMDV 2B modulates host IFN signal pathway by the degradation of RIG-I and MDA5. FMDV 2B targeted the RIG-I for ubiquitination and proteasomal degradation by recruiting E3 ubiquitin ligase ring finger protein 125 (RNF125) and also targeted MDA5 for apoptosis-induced caspase-3- and caspase-8-dependent degradation. Ultimately, FMDV 2B significantly inhibited RNA virus-induced IFN-β production. Importantly, we identified that the C-terminal amino acids 126-154 of FMDV 2B are essential for 2B-mediated degradation of the RIG-I and MDA5. Collectively, these results provide a clearer understanding of the specific molecular mechanisms used by FMDV 2B to inhibit the IFN responses and a rational approach to virus attenuation for future vaccine development.

show abstract

Inhibition of MAVS Aggregation-Mediated Type-I Interferon Signaling by Foot-and-Mouth Disease Virus VP3

Cited by 10 publications

References 66 publications

Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells

Identification of Orbivirus Non-Structural Protein 5 (NS5), Its Role and Interaction with RNA/DNA in Infected Cells

Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling

Foot-and-mouth disease virus non-structural protein 2B downregulates the RLR signaling pathway via degradation of RIG-I and MDA5

Contact Info

Product

Resources

About