# The Roles of FRCs In HIV-1 Spread And Establishment Of Latency

> **NIH NIH R21** · EAST CAROLINA UNIVERSITY · 2024 · $226,500

## Abstract

Secondary lymphoid organs including lymph nodes (LNs) are a major site for HIV-1 spread. Furthermore,
secondary lymphoid organs harbor viral reservoirs, which are a barrier to curing AIDS. Follicular helper T cells
and follicular dendritic cells in B cell follicles are well studied as viral reservoirs in LNs. Notably, in addition to B
cell follicles, T cell zones (TCZs) within LNs contain bona fide latent and persistent viral reservoirs in antiretroviral
therapy-suppressed HIV-1 patients. However, despite the potential of TCZs as a source of viral reservoirs, how
HIV-1 disseminates and how viral reservoirs are generated in TCZs are poorly understood. In this application,
we propose to determine the effect of TCZ fibroblastic reticular cells (TRCs) on HIV-1 and SIV spread and latency
establishment. We previously demonstrated that TRCs isolated from human LNs mediate trans-infection of HIV-
1 and that the interaction between hyaluronan (a polysaccharide) and CD44 plays a key role in this process.
Additionally, our preliminary experiments showed that TRCs render resting CD4+ T cells, the most abundant cell
group in TCZs, permissive to both productive and latent infection when the T cells are cocultured with TRCs prior
to infection. Therefore, it is possible that the interactions between resting CD4+ T cells and TRCs promote HIV-
1 spread by two mechanisms, i.e., enhancing of permissiveness to HIV-1 infection and mediating trans-infection.
However, it is unknown whether TRCs mediate trans-infection of HIV-1 through CD44-hyaluronan interactions
in vivo and how TRCs enhance the permissiveness of resting CD4+ T cells to productive and latent infection. We
will investigate whether TRCs isolated from rhesus macaque LNs mediate trans-infection of SIV via CD44-
hyaluronan interactions ex vivo. This investigation allows us to determine the extent of conservation of the trans-
infection mechanism described above and the usefulness of an in vivo SIV/rhesus macaque model for studies
of TRC-dependent HIV-1 spread in secondary lymphoid organs. Additionally, we will identify the TRC factors
that render resting CD4+ T cells permissive to HIV-1 infection and define the roles of TRCs in latency
establishment in TCZs. Completion of the proposed research establishes the basis for a mechanistic
understanding of the roles of TRCs in HIV dissemination and latency and could contribute to the development of
a strategy inhibiting latency establishment.

## Key facts

- **NIH application ID:** 11135806
- **Project number:** 7R21AI179288-02
- **Recipient organization:** EAST CAROLINA UNIVERSITY
- **Principal Investigator:** Tomoyuki Murakami
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $226,500
- **Award type:** 7
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11135806

## Citation

> US National Institutes of Health, RePORTER application 11135806, The Roles of FRCs In HIV-1 Spread And Establishment Of Latency (7R21AI179288-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/11135806. Licensed CC0.

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