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SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef

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  • Yoshiko Usami

    (Cell and Cancer Biology, University of Massachusetts Medical School)

  • Yuanfei Wu

    (Cell and Cancer Biology, University of Massachusetts Medical School)

  • Heinrich G. Göttlinger

    (Cell and Cancer Biology, University of Massachusetts Medical School)

Abstract

HIV-1 Nef and the unrelated mouse leukaemia virus glycosylated Gag (glycoGag) strongly enhance the infectivity of HIV-1 virions produced in certain cell types in a clathrin-dependent manner. Here we show that Nef and glycoGag prevent the incorporation of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and SERINC5 into HIV-1 virions to an extent that correlates with infectivity enhancement. Silencing of both SERINC3 and SERINC5 precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. The infectivity of nef-deficient virions increased more than 100-fold when produced in double-knockout human CD4+ T cells that lack both SERINC3 and SERINC5, and re-expression experiments confirmed that the absence of SERINC3 and SERINC5 accounted for the infectivity enhancement. Furthermore, SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. SERINC3 and SERINC5 are highly expressed in primary human HIV-1 target cells, and inhibiting their downregulation by Nef is a potential strategy to combat HIV/AIDS.

Suggested Citation

  • Yoshiko Usami & Yuanfei Wu & Heinrich G. Göttlinger, 2015. "SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef," Nature, Nature, vol. 526(7572), pages 218-223, October.
    • Handle: RePEc:nat:nature:v:526:y:2015:i:7572:d:10.1038_nature15400
    DOI: 10.1038/nature15400
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    Cited by:

    1. Sunan Li & Rongrong Li & Iqbal Ahmad & Xiaomeng Liu & Silas F. Johnson & Liangliang Sun & Yong-Hui Zheng, 2022. "Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Susan A. Leonhardt & Michael D. Purdy & Jonathan R. Grover & Ziwei Yang & Sandra Poulos & William E. McIntire & Elizabeth A. Tatham & Satchal K. Erramilli & Kamil Nosol & Kin Kui Lai & Shilei Ding & M, 2023. "Antiviral HIV-1 SERINC restriction factors disrupt virus membrane asymmetry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Uddhav Timilsina & Supawadee Umthong & Emily B. Ivey & Brandon Waxman & Spyridon Stavrou, 2022. "SARS-CoV-2 ORF7a potently inhibits the antiviral effect of the host factor SERINC5," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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