Localization to detergent-resistant membranes and HIV-1 core entry inhibition correlate with HIV-1 restriction by SERINC5

Bianca Schulte, Anastasia Selyutina, Silvana Opp, Alon Herschhorn, Joseph G. Sodroski, Massimo Pizzato, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

SERINC5(S5) is a multi-span transmembrane protein that potently blocks the infectivity of HIV-1 produced by human T-cells. The ability of S5 to restrict infectivity correlates with its presence in the virion, but the exact mechanism by which S5 restricts HIV-1 is unknown. Here we tested whether the core from HIV-1 virions containing S5 is delivered to the cytoplasm. Using the “fate of the capsid” assay, we demonstrated that the viral core of S5-restricted HIV-1 does not reach the cytoplasm of target cells, suggesting a block in the delivery of the core to the cytoplasm. In agreement with evidence suggesting that the viral determinants for S5 restriction map to the envelope of HIV-1, we observed that S5 induces conformational changes to the HIV-1 envelope. Further, we demonstrated that S5 localizes to detergent-resistant membranes (DRMs), as has been shown previously for the HIV-1 envelope in producer cells. In order to identify the determinants of S5 restriction, we explored the ability of all human SERINC proteins to restrict HIV-1. In contrast to human S5, we observed that human SERINC2(S2) did not restrict HIV-1, and was inefficiently incorporated into HIV-1 virions when compared to S5. Experiments using S5-S2 chimeric proteins revealed two functional domains for restriction: one necessary for S5 incorporation into virions, which does not seem to be necessary for restriction, and a second one necessary to change the HIV-1 envelope conformation, localize to DRMs, and block infection.

Original languageEnglish (US)
Pages (from-to)52-65
Number of pages14
JournalVirology
Volume515
DOIs
StatePublished - Feb 2018

Keywords

  • Core
  • DRMs
  • Envelope
  • HIV-1
  • Restriction
  • SERINC2
  • SERINC5

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Localization to detergent-resistant membranes and HIV-1 core entry inhibition correlate with HIV-1 restriction by SERINC5'. Together they form a unique fingerprint.

  • Cite this