# Role of viral tropism in molecular signatures of HIV latency

> **NIH NIH R56** · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2021 · $592,946

## Abstract

The latent reservoir remains the major obstacle to a cure for HIV/AIDS. Results from recent reports are
consistent with the idea that the HIV reservoir cannot be accurately defined using expression of a single
protein. The reported protein profiles also showed donor-dependent attributes. Better understanding is needed
of what factors contribute to heterogeneity of the reservoir signatures. Our long-term goal is to develop
strategies to target latently infected cells for elimination. The specific objective of the proposed research is to
determine the contribution of viral tropism to molecular signatures of the latenly infected cells. Our central
hypothesis is that cells latently infected with HIV will have both shared and unique molecular signatures when
infected with CCR5- or CXCR4-tropic virus, tied to the phenotypic composition of infected cells. The rationale
of the proposed research is to provide a molecular platform for the future development of improved strategies
of reservoir targeting using antibody-based approaches, or optimization of latency reversal. We will test our
central hypothesis by pursuing the following specific aims: 1) Determine how CCR5- and CXCR4-tropic
infection in phenotypically different CD4+ T cells affects the characteristics of the latent reservoir; 2) Identify
molecular signatures of CD4+ T cells infected with virus of different tropism; 3) Determine contribution of
tropism-dependent cell markers to the performance of antibody panels to capture latently infected cells from
persons with HIV. The novel aspect of our proposal is the focus on three major reservoir subsets: established
in naïve cells, established in naïve cells that transitioned to memory, and established in memory cells, in the
context on CXCR4- and CCR5-tropic infection. We will characterize integration frequencies and
responsiveness of the reservoir to latency reversing agents (LRAs) in vitro, and identify phenotypic differences
at the protein and RNA level between latently infected and uninfected cells individually within each of these
subsets. The latest innovations in liquid chromatography mass spectrometry and single cell RNA sequencing
will be used. Peripheral blood and tissue samples from persons with HIV will be used to determine the
contribution of tropism-specific signatures of latency to the efficiency of reservoir capture ex vivo. We expect
that using no more than 15 antibodies, at least 70-90% of the latent reservoir will be captured, but different
antibody panels may be needed depending on the tropism of the virus infecting each individual. Our proposed
multidisciplinary efforts will reveal the complete molecular signatures of cells of different phenotypic subsets
infected with virus of different tropism. This research will be important for people with HIV, because it
represents a significant step towards achieving the ultimate goal to reduce the latent reservoir size to the levels
at which viral suppression can be sustained upon cessation...

## Key facts

- **NIH application ID:** 10434386
- **Project number:** 1R56AI157755-01A1
- **Recipient organization:** VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
- **Principal Investigator:** Nadejda S Beliakova-Bethell
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $592,946
- **Award type:** 1
- **Project period:** 2021-07-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434386

## Citation

> US National Institutes of Health, RePORTER application 10434386, Role of viral tropism in molecular signatures of HIV latency (1R56AI157755-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10434386. Licensed CC0.

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