Epigenetic Mechanisms Regulating HIV CNS Latency and Neuropathogenesis Using Novel Single Cell Technologies (R21 Clinical Trial Not Allowed) | RFA MH 22 281

Opportunity Information: Apply for RFA MH 22 281

This funding opportunity, RFA-MH-22-281, is a discretionary National Institutes of Health (NIH) research grant announcement that uses the R21 mechanism and specifically does not allow clinical trials. Its central purpose is to support exploratory, early-stage research focused on how epigenetic processes influence HIV latency and HIV-related disease processes in the central nervous system (CNS). The scientific emphasis is on understanding the molecular and regulatory "switches" that help HIV persist in the brain and contribute to neurological injury, even in the context of modern treatment, by looking closely at epigenetic regulation in brain-derived cell populations that are relevant to HIV infection and inflammation.

The core research target is HIV CNS latency and neuropathogenesis in specific brain-resident or brain-associated cell types, especially macrophages, microglia, and astrocytes. These cells are repeatedly highlighted because they are strongly implicated in CNS viral persistence, neuroinflammation, and downstream neurological complications. The opportunity encourages projects that move beyond bulk-tissue averages and instead resolve heterogeneity at the level of individual cells, with an expectation that applicants will use novel single-cell technologies to map and interpret epigenetic states. In practical terms, this points toward approaches such as single-cell and single-nucleus profiling methods that can capture cell-to-cell variation in chromatin accessibility, DNA methylation, histone modifications, transcriptional programs, or multi-omic combinations that connect epigenetic regulation with gene expression in the same cells.

A key element of the announcement is its framing around epigenetic mechanisms as drivers or maintainers of HIV latency in the CNS and as contributors to neuropathogenesis. Epigenetic regulation refers to chemical and structural changes that affect gene activity without changing the underlying DNA sequence, and in the context of HIV it includes how chromatin structure and regulatory marks can silence or permit viral transcription, influence host inflammatory pathways, and shape cellular phenotypes linked to viral persistence. By requiring or strongly encouraging single-cell level interrogation, the FOA is essentially pushing the field toward higher-resolution mechanistic understanding: identifying which subpopulations of microglia or macrophages may harbor latent virus, which epigenetic patterns correlate with reactivation potential, and which regulatory programs are associated with neurotoxic or neuroprotective responses.

From an administrative standpoint, the activity category is health research and the listed CFDA numbers are 93.242 and 93.853. The funding instrument is a grant, and the eligible applicant pool is broad. It includes a wide range of U.S. governmental entities (state, county, city/township, special district governments), public and independent school districts, public housing authorities/Indian housing authorities, and federally recognized tribal governments. It also includes higher education institutions (public/state-controlled and private), nonprofits with and without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories), for-profit organizations other than small businesses, and small businesses. In addition, the announcement explicitly calls out eligibility for several institution types and organizational categories often emphasized in federal research programs, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), non-federally recognized tribal governments, eligible federal agencies, faith-based or community-based organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations) as well as regional organizations.

The opportunity was created on 2022-07-11 and had an original closing date of 2022-12-05, reflecting a defined submission window for that cycle. While the source data you provided does not specify an award ceiling or expected number of awards, the R21 mechanism generally signals that the program is oriented toward innovative, higher-risk ideas, feasibility work, and proof-of-concept studies rather than large, long-duration projects. In that spirit, strong applications would typically be expected to present a compelling, well-justified biological question about epigenetic regulation of HIV persistence or CNS disease processes, paired with a rigorous single-cell strategy capable of teasing apart diverse brain cell populations and revealing mechanistic links between epigenetic state, viral latency, and neuropathogenic pathways, all without proposing a clinical trial.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Epigenetic Mechanisms Regulating HIV CNS Latency and Neuropathogenesis Using Novel Single Cell Technologies (R21 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242, 93.853.
• This funding opportunity was created on 2022-07-11.
• Applicants must submit their applications by 2022-12-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA MH 22 281

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