# Elucidating the role of B cell mediated trans infection in the establishment of the latent HIV-1 reservoir

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $778,686

## Abstract

SUMMARY
HIV-1 can proliferate through both the release of cell-free particles (cis-infection) and by cell-to-cell
transmission (trans-infection). Prior studies have shown that HIV-1 trans-infection: (i) is significantly more
efficient than cis-infection; (ii) can efficiently infect resting CD4+ T cells, which are inherently resistant to cis-
infection; and (iii) is largely insensitive to inhibition by antiretroviral therapy (ART). Consequently, HIV-1 trans-
infection is thought to play a key role in the pathogenesis of HIV-1 infection. Direct evidence of HIV-1 trans-
infection in vivo, however, is lacking! Our group was the first to demonstrate that activated B cells express the
C-type lectin DC-SIGN and have the ability to sequester and then efficiently transfer HIV-1 to bystander
CD4+T cells. B cells have a greater capacity to transfer HIV-1 to CD4+ T cells than other antigen presenting
cells, including dendritic cells (DCs) and macrophages. We recently found that B cells, but not immature or
mature DC, also have the unique ability to efficiently trans-infect CD4+ naïve (TN) cells – which do not express
the CCR5 receptor – with R5-tropic HIV-1. Importantly, we have reported that B cells from HIV-infected
nonprogressors (NPs, individuals who control viremia in the absence of ART) do not support HIV-1 trans-
infection of CD4+ T cells. Consistent with these findings, purified CD4+ TN cells isolated from NPs harbor a
very small (or even negligible) reservoir of total HIV-1 DNA, compared to ART-treated progressors. In this R01
application, our overarching hypothesis is that B lymphocyte-mediated cell-to-cell HIV-1 trans-infection
contributes to the establishment and replenishment of the latent viral reservoir in resting CD4+ T cells, in
particular CD4+ TN and T follicular helper cells. We propose to use novel state-of the-art approaches to
investigate this hypothesis, and expect to provide the first evidence that HIV-1 trans-infection plays a key role
in viral pathogenesis.

## Key facts

- **NIH application ID:** 10402053
- **Project number:** 1R01AI162615-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** NICOLAS PAUL SLUIS-CREMER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $778,686
- **Award type:** 1
- **Project period:** 2022-08-02 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402053

## Citation

> US National Institutes of Health, RePORTER application 10402053, Elucidating the role of B cell mediated trans infection in the establishment of the latent HIV-1 reservoir (1R01AI162615-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10402053. Licensed CC0.

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