# SERINCs and Nef Function

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $418,750

## Abstract

ABSTRACT
The accessory HIV-1 protein Nef is a major pathogenicity determinant that is crucial for high
virus loads and for progression to AIDS. Nef increases the specific infectivity of HIV-1 virions,
but the mechanism has long remained enigmatic. We have recently identified the multipass
transmembrane proteins SERINC3 and SERINC5 as novel anti-viral factors whose down-
regulation by Nef accounts for its effect on HIV-1 infectivity. SERINC5 in particular strongly
inhibits the infectivity of Nef-deficient HIV-1 progeny virions. HIV-1 Nef induces the removal of
SERINC3 and SERINC5 from the surface of virus-producing cells, which prevents their
incorporation into HIV-1 virions and consequently counteracts their inhibitory effects on HIV-1
infectivity. However, it remains unclear how SERINCs affect HIV-1 virions. We propose to
investigate what determines the susceptibility of HIV-1 envelope glycoproteins to SERINCs,
whether SERINCs account for the ability of Nef to protect a membrane-proximal region of gp41,
and whether SERINCs affect the viral lipid envelope. It also remains unclear what step during
the early phase of HIV-1 replication is inhibited by virion-associated SERINCs. We propose to
investigate the hypothesis that SERINCs inhibit the translocation of the mature viral core into
target cells. Finally, we propose to investigate what step of SERINC trafficking is affected by
Nef, and what determines the ability of Nef to selectively downregulate those SERINC family
members that inhibit HIV-1. These studies are significant, because SERINC3 and SERINC5 are
highly expressed in primary HIV-1 target cells. Inhibiting their downregulation by Nef is thus a
potential strategy to combat HIV/AIDS.

## Key facts

- **NIH application ID:** 9915890
- **Project number:** 5R01AI127263-05
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** HEINRICH GOTTLINGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2016-06-13 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915890

## Citation

> US National Institutes of Health, RePORTER application 9915890, SERINCs and Nef Function (5R01AI127263-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9915890. Licensed CC0.

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