Title

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

UMMS Affiliation

Department of Molecular, Cell and Cancer Biology

Date

10-8-2015

Document Type

Article

Disciplines

Cell Biology | Immunology of Infectious Disease | Immunoprophylaxis and Therapy

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.

Rights and Permissions

Citation: Nature. 2015 Oct 8;526(7572):218-23. doi: 10.1038/nature15400. Epub 2015 Sep 30. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

26416733