# MARCH Proteins, Members of a Host Protein Family that Targets HIV-1

> **NIH NIH R56** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $391,890

## Abstract

Project Summary/ Abstract
Membrane Associated RING CH (MARCH) proteins are RING E3 ubiquitin ligases that are implicated in the
regulation of membrane receptors. This family of ubiquitin ligases emerged after the discovery of K3 and K5, two
viral MARCH-homologues in Kaposi’s sarcoma associated herpesvirus (KSHV), which are critical in evading the
host’s immune response by ubiquitinating and subsequently removing the major histocompatibility complex class
II (MHC-II) receptors from the surface of the cells and therefore blocking antigen presentation. The cellular
MARCH family of proteins consists of 11 members that share structural similarity and contain a RING-CH domain
that is essential for the removal and internalization of target membrane receptors (e.g. MHC-II). Recent reports
showed that MARCH proteins can also potently restrict human immunodeficiency virus 1 (HIV-1) infection.
MARCH1, 2 and 8 restrict HIV-1 and other retroviruses by blocking the incorporation of the viral envelope in the
budding virions. This proposal explores aspects of the MARCH-mediated antiretroviral mechanism that have
never been previously studied. Currently, there is no information concerning a viral protein that counteracts
MARCH proteins. The first aim of this research plan examines the mechanism by which an HIV encoded factor
counteracts MARCH8 during infection. The second aim examines the susceptibility of HIV-1 envelopes from
different subtypes to MARCH-mediated restriction as well as the ability of HIV-1 proteins from different subtypes
to counteract MARCH8. Preliminary studies show that HIV-1 over time becomes resistant to MARCH restriction.
The third aim will determine the changes in the HIV-1 genome that render it resistant to MARCH inhibition.
Finally, the fourth aim will address the role of the other MARCH proteins on HIV-1 infection. In summary, these
studies will shed new light on the anti-retroviral role of MARCH proteins and will address aspects of MARCH-
mediated HIV-1 inhibition that have not been previously determined. Finally, these proteins have strong potential
as clinical targets for the development of antiretroviral therapeutics.

## Key facts

- **NIH application ID:** 10455259
- **Project number:** 1R56AI165161-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Spyridon Stavrou
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $391,890
- **Award type:** 1
- **Project period:** 2021-08-12 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455259

## Citation

> US National Institutes of Health, RePORTER application 10455259, MARCH Proteins, Members of a Host Protein Family that Targets HIV-1 (1R56AI165161-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10455259. Licensed CC0.

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