# HIV-1-dependent HERV-K proteome

> **NIH NIH R21** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $211,875

## Abstract

Abstract
During infection, part of the cellular environment rewired by HIV-1 is composed by endogenous retroviruses.
Studies that have revealed the HIV mediated increase of HERV-K HML-2 proteins, underscored HERV-K
potential as an excellent source of antigenic targets for anti-HIV therapy. We have found that during HIV-1
infection of primary CD4+ T-cells, the high expressing HERV-K HML-2 elements are those that are unable to
autonomously produce proteins. This creates a conundrum about which are the elements that are at the root of
HIV-1 dependent HERV-K HML-2 protein production and by what mechanism they achieve it. We will
investigate the mechanism by which HIV-1 mediates HERV-K HML-2 protein upregulation during infection.
Furthermore, the repetitive nature of HERV-K HML-2 family has undermined their study in relation to the effect
they have on HIV-1, as conventional analysis systems are often insufficient. By combining HERV-K-specific
RNA and protein expression analyses we have devised an approach that not only can accurately establish the
HERV-K expression profile of different cell types, but also determines which of those expressed HERV-Ks
produces proteins and peptides. The identity of the specific elements responsible for HERV-K HML-2 protein
expression is essential to investigate the consequences of their expression on HIV-HERV-K interaction, as
small differences in amino acid sequence have been demonstrated to have important repercussions on their
function. Taken together, this proposal will contribute to a better understanding of the relation between HIV-1
infection and HERV-K protein production, and provide the tools to assess specific HERV-K HML-2 as potential
HIV-1-dependent antigenic targets for antiviral therapy.

## Key facts

- **NIH application ID:** 10114204
- **Project number:** 5R21AI150355-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** LUBBERTUS C MULDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2020-02-25 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114204

## Citation

> US National Institutes of Health, RePORTER application 10114204, HIV-1-dependent HERV-K proteome (5R21AI150355-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10114204. Licensed CC0.

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