期刊
SCIENCE SIGNALING
卷 14, 期 700, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.abc7611
关键词
-
资金
- NIH [R01 AI112381, R01 AI150473, R01GM120496, R01GM135234]
- Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH
SERINC3 and SERINC5, known as host restriction factors against HIV, were found to exhibit additional antiviral activities by enhancing the expression of genes encoding type I interferons and nuclear factor kappa B signaling. SERINC5 interacts with MAVS and TRAF6, leading to enhancement of antiviral activities and inhibition of HIV-1 and rVSV infection. These findings suggest a novel function of SERINC proteins in modulating host inflammatory signaling and antiviral responses.
The SERINC (serine incorporator) proteins are host restriction factors that inhibit infection by HIV through their incorporation into virions. Here, we found that SERINC3 and SERINC5 exhibited additional antiviral activities by enhancing the expression of genes encoding type I interferons (IFNs) and nuclear factor kappa B (NF-kappa B) signaling. SERINC5 interacted with the outer mitochondrial membrane protein MAVS (mitochondrial antiviral signaling) and the E3 ubiquitin ligase and adaptor protein TRAF6, resulting in MAVS aggregation and polyubiquitylation of TRAF6. Knockdown of SERINC5 in target cells increased single-round HIV-1 infectivity, as well as infection by recombinant vesicular stomatitis virus (rVSV) bearing VSV-G or Ebola virus (EBOV) glycoproteins. Infection by an endemic Asian strain of Zika virus (ZIKV), FSS13025, was also enhanced by SERINC5 knockdown, suggesting that SERINC5 has direct antiviral activities in host cells in addition to the indirect inhibition mediated by its incorporation into virions. Further experiments suggested that the antiviral activity of SERINC5 was type I IFN-dependent. Together, these results highlight a previously uncharacterized function of SERINC proteins in promoting NF-kappa B inflammatory signaling and type I IFN production, thus contributing to its antiviral activities.
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