SERINC proteins potentiate antiviral type I IFN production and proinflammatory signaling pathways

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...

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Bibliographic Details
Published in:Science signaling 2021-09, Vol.14 (700), p.eabc7611-eabc7611
Main Authors: Zeng, Cong, Waheed, Abdul A, Li, Tianliang, Yu, Jingyou, Zheng, Yi-Min, Yount, Jacob S, Wen, Haitao, Freed, Eric O, Liu, Shan-Lu
Format: Article
Language:English
Subjects:
Adapters
Adaptor proteins
Antiviral activity
Antiviral Agents
Cytokines
Gene expression
Genes
Glycoproteins
HIV
Human immunodeficiency virus
Incorporation
Infections
Infectivity
Inflammation
Interferon
Membrane proteins
Membranes
Mitochondria
NF-κB protein
Oligomerization
Proteins
Signal Transduction
Signaling
Stomatitis
TRAF6 protein
Transcription activation
Ubiquitin
Ubiquitin-protein ligase
Vector-borne diseases
Viral diseases
Viral infections
Virions
Viruses
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Summary: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 κB (NF-κB) 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-κB inflammatory signaling and type I IFN production, thus contributing to its antiviral activities.
ISSN:1945-0877
1937-9145
DOI:10.1126/scisignal.abc7611