# HIV-2 latency and its reversal

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $905,874

## Abstract

Abstract
 The lentiviruses HIV-1 and HIV-2 cause acquired immunodeficiency syndrome (AIDS) in humans. The
conventional wisdom that HIV-2 is a more benign cousin to HIV-1 was recently challenged, however, in a large
study that found after 23 years of HIV-2 infection, cumulatively over 90% of participants had AIDS and 80% had
died. An effective, safe, and scalable cure for HIV should account for any unique features that may characterize
HIV-2 latency.
 During the course of its replication, HIV-2 integrates into human DNA and creates a reservoir that is a
barrier to virus eradication - as is the problem for HIV-1. How similar, or different, these HIV reservoirs may be
is unknown. The scientific premise of this proposal is that there are unrecognized unique features of HIV-2
biology that may impact virus eradication efforts, relative to HIV-1. As an example, the HIV-2 Vpx protein has
recently been shown to counteract the Human Silencing Hub (HUSH), a highly conserved gene silencing
complex known to repress HIV-1 proviruses, in ways that may impact virus latency and the reservoir landscape.
HIV-2 vpx reactivates latent provirus transcription in primary human CD4+ T cells through degradation of the
HUSH complex.
 To study HIV-2 latency, we have recruited participants with HIV-2 into our longitudinal HIV Eradication
and Latency (HEAL) cohort. Our HIV-2 proviral landscape preliminary data has identified differences between
the HIV-1 and HIV-2 proviral landscapes and we see phylogenetic evidence that suggests clonal expansion may
maintain the HIV-2 reservoir, findings we propose to explore further in this proposal. We hypothesize that HIV-2
latency reversal differs from HIV-1 reactivation, provide data to support this, and propose experiments to
investigate the mechanisms that may explain these observations.
 The goal of this proposal is to use HIV and host genomic information to define the landscape of HIV-2
integration and investigate the mechanisms that control HIV-2 latency and its reversal. Here we propose to
leverage cutting-edge techniques to address important knowledge gaps in our understanding of HIV-2 infection
biology. We hypothesize that HIV-2 differs from HIV-1 in integration landscape and reversal from latency and
that Vpx plays a key role in these differences. Specific Aims of this proposal are to define the HIV-2 integration
landscape in vivo, understand the role of HIV-2 vpx in virus latency, and investigate the transcriptional blocks to
HIV-2 latency reversal. Our approaches test hypotheses that are central to understand HIV-2 latency and its
reversal.

## Key facts

- **NIH application ID:** 10491971
- **Project number:** 5R01AI155131-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Athe M. Tsibris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $905,874
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491971

## Citation

> US National Institutes of Health, RePORTER application 10491971, HIV-2 latency and its reversal (5R01AI155131-02). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10491971. Licensed CC0.

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