# Harnessing the Pathogenesis of CMV Against HIV

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $467,055

## Abstract

PROJECT SUMMARY/ABSTRACT
CD8+ cytotoxic T lymphocytes (CTLs) play a key role protective role in HIV-1 infection, but cannot fully
suppress the virus because they require antigen for maintenance. HIV-1-specific CTLs mediate the
suppression of HIV-1 for the “asymptomatic” phase of chronic infection. The CTL response partially controls
infection, but once the antigen is cleared to very low levels, they decay to low frequency resting central
memory cells. Since CTLs require antigen to maintain effector function, they cannot fully suppress even in
most “elite controllers,” who exhibit pathogenic low level infection. To suppress HIV-1 fully, CTLs need to be
maintained independently of HIV-1 replication.
Cytomegalovirus (CMV) drives CTL persistence through frequent low grade reactivations. Frequent
spontaneous non-pathogenic reactivations of CMV drive persistent maintenance of CMV-specific active
effector CTLs.
We hypothesize that creating CTLs recognizing both CMV and HIV-1 can yield superior control of HIV-1
infection. Such CTLs would be maintained by natural CMV reactivations to be primed as active effector cells
against HIV-1. To achieve this goal, we have developed a prototype bi-specific chimeric antigen receptor
(CAR) that recognizes both CMV and HIV-1, coupling maintenance to CMV and de-coupling maintenance from
HIV-1. This project will expand that effort; specifically we aim:
 1. To optimize a panel of CMV and HIV-1 bi-specific CARs;
 2. To evaluate the function of these CARs in the BLT humanized mouse model.

## Key facts

- **NIH application ID:** 11005914
- **Project number:** 1R01AI181579-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** OTTO O YANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $467,055
- **Award type:** 1
- **Project period:** 2024-07-22 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11005914

## Citation

> US National Institutes of Health, RePORTER application 11005914, Harnessing the Pathogenesis of CMV Against HIV (1R01AI181579-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11005914. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*