# Microbiome and Mucosal Immune Interactions in the Pathogenesis of HIV-1 Transmission

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $154,148

## Abstract

PROJECT SUMMARY / ABSTRACT
Mucosal HIV-1 transmission accounts for the majority of new HIV infections, yet is a poorly understood event.
Clinical and experimental evidence supports the role of local immune activation and inflammation in facilitating
HIV-1 transmission. The immunologic factors contributing to this phenomenon are an area of intense interest.
The intestinal microbiome consists of a diverse collection of organisms, many of which influence mucosal
inflammation and immunity. Alterations in the microbiome, termed dysbiosis, have been associated with HIV-1
infection, yet the drivers of these dysbiosis and its effect on HIV susceptibility remain unclear. Substance use is
known to increase risk of HIV-1 acquisition and alter the gut microbiome, and its study therefore offers an
opportunity to examine a mechanistic link between a defined environmental factor and HIV-1 transmission
through effects on the microbiome and/or mucosal immunity. We hypothesize that increased HIV-1 acquisition
risk due to substance use results from pro-inflammatory alterations of the intestinal microbiome and/or direct
effects on the inflammatory state of the mucosa, thereby increasing HIV-1 susceptibility. This proposal aims to
investigate this hypothesis by characterizing the intestinal microbiome using a unique cohort of young men
who have sex with men (MSM) who are HIV-1 seropositive or at-risk. Our study has the unique advantage of
specimens coupled with detailed clinical, substance use, and sexual behavior data which will allow us to
address influence of these factors on dysbiosis and mucosal inflammation. Using these specimens, we can
employ novel ex vivo assays to directly examine the mechanisms mediating microbiome effects on mucosal
immune activation and HIV-1 susceptibility. Specifically, we propose to: 1) characterize the impact of risk
factors such as substance use on the intestinal microbiome in HIV-positive and at-risk individuals, 2) examine
the mucosal activation status and its relationship to dysbiosis in at-risk individuals, and 3) optimize mucosal
HIV-1 infection assays to quantitate susceptibility of gut mucosa. These findings may reveal potentially
modifiable targets to improve HIV-1 prevention strategies in certain at-risk populations.
This career development award application will support the training, mentoring, and research of a promising
junior investigator. The environment offers the combination of exceptional faculty and staff, state-of-the-art
resources and facilities, and an institutional commitment to research which all serve to foster the success of
this research project and career development plan. The proposed research will allow the applicant to receive
specific advanced training in the following focused areas: 1) bioinformatics and computational methods, 2)
advanced statistics, 3) mucosal immunology and microbiology, and 4) academic scientific research. The
training plan includes a combination of directed didactic training and m...

## Key facts

- **NIH application ID:** 10105282
- **Project number:** 5K08AI124979-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jennifer Fulcher
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $154,148
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105282

## Citation

> US National Institutes of Health, RePORTER application 10105282, Microbiome and Mucosal Immune Interactions in the Pathogenesis of HIV-1 Transmission (5K08AI124979-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10105282. Licensed CC0.

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