# Defective HIV proviruses and Persistent Innate Immune Activation

> **NIH NIH R01** · BOSTON MEDICAL CENTER · 2024 · $765,274

## Abstract

Abstract/Summary
CD4+ T cells and macrophages are infected by HIV and this infection correlates to more proinflammatory
activities that drive HIV comorbidities and end organ diseases. Mechanisms that bias innate immune functions
in HIV-infected cells towards chronic inflammation are poorly understood. We have demonstrated infected
primary resting CD4+ T cells and macrophages harbor defective HIV-1 proviruses that, despite having deletions
and mutations which attenuate provirus transcription, generate HIV-1 RNAs. The immunopathological
consequences of persistent aberrant viral RNA expression have not been addressed. We hypothesize that HIV
infection of CD4+ T cells and macrophages establishes a defective but transcriptionally competent
proviral reservoir that expresses aberrant viral RNAs which perpetuate persistent inflammation. We will
address this hypothesis in three specific aims: 1) Determine if persistent expression of cryptic HIV-1 RNAs
promote innate immune activities; 2) Examine whether HIV-1 and HIV-2 have different propensities for
generating intact proviral genomes and whether this influences immune activation; and 3) Determine if DNA
damage response mechanisms lead to establishment of defective proviruses. Successful completion of these
studies will provide general insights into the impact of HIV-1 persistence and expression in the context of CD4+
T cells and macrophages. Importantly, these studies will provide an understanding into mechanisms that
contribute to HIV-1 comorbidities which persist even with antiretroviral treatments and could lead to new targets
and strategies for treatments to improve the lives of people living with HIV.

## Key facts

- **NIH application ID:** 11020156
- **Project number:** 1R01AI187175-01
- **Recipient organization:** BOSTON MEDICAL CENTER
- **Principal Investigator:** SURYARAM GUMMULURU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $765,274
- **Award type:** 1
- **Project period:** 2024-08-22 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11020156

## Citation

> US National Institutes of Health, RePORTER application 11020156, Defective HIV proviruses and Persistent Innate Immune Activation (1R01AI187175-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11020156. Licensed CC0.

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