# Innate immune memory promotes neural damage in the ART suppressed HIV infected brain

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $566,979

## Abstract

ABSTRACT
The widespread use of antiretroviral therapy (ART) in developed countries has modified HIV infection from a
terminal illness to what is now largely a manageable chronic infection. Even when HIV replication is suppressed
with ART, people infected with HIV present with a chronic inflammatory state that is thought to contribute to the
development of neurologic and psychiatric co-morbid conditions. A growing body of evidence is implicating the
innate immune system with sensitization of the brain to neurological damage associated with HIV infection and
other neurodegenerative conditions. This non-resolving inflammatory/immune response sensitizes and primes
the brain for any subsequent inflammatory event, and is thought to be a form of innate immune memory in which
microglia adapt their phenotype depending on the stimulus they are exposed to, and the frequency with which
they are exposed to that stimulus. This adaptation is a form of innate immune memory that can be associated
with long-lasting molecular reprogramming that can either enhance or suppress the microglial response to
subsequent stimuli. The impact of HIV infection, and ART on microglial reprogramming is unknown. Here we
have identified the sphingomyelin hydrolase neutral sphingomyelinase2 (nSMase2) generated ceramide as a
critical regulator of the innate immune response to ART suppressed HIV infection.

## Key facts

- **NIH application ID:** 10854974
- **Project number:** 5R01MH131219-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** VALINA L. DAWSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $566,979
- **Award type:** 5
- **Project period:** 2022-09-09 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854974

## Citation

> US National Institutes of Health, RePORTER application 10854974, Innate immune memory promotes neural damage in the ART suppressed HIV infected brain (5R01MH131219-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10854974. Licensed CC0.

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