# Project 1: Microbiota-mediated defense against viral infection following SCT

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $386,021

## Abstract

Abstract
Cytomegalovirus (CMV) and respiratory virus infections are common causes of morbidity and
mortality following allo-HCT. Recent studies in animal models demonstrated that the intestinal
microbiota contributes to anti-viral resistance. Our studies demonstrate that loss of bacterial
diversity in fecal microbiota of allo-HCT patients at the time of stem cell engraftment is associated
with higher rates of viral infections in the post-engraftment period and that loss of butyrate-
producing commensal bacteria increases the risk of viral lower respiratory tract infection (LRTI).
Our goal is to determine whether members of the intestinal microbiota contribute to antiviral
resistance and to eventually modify microbiota composition and diversity to optimize resistance
against viral infection and reactivation. The first aim is to correlate fecal microbiota composition
following allo-HCT with risk of sustained CMV viremia and to extend our studies demonstrating
that loss of butyrate-producing commensal bacteria increases the risk of LRTI. We will investigate
CMV seropositive patients following allo-HCT and correlate the intestinal microbiome with risk of
protracted, high-level CMV viremia following engraftment. The second aim will determine whether
microbiota from allo-HCT patients who either developed severe viral infections or maintained a
high level of resistance, upon transplantation into germ free (GF) mice, determines
resistance/susceptibility to MCMV and Influenza Virus infection. The third aim is to test specific
commensal species in gnotobiotic mice for their ability to confer resistance to viral infections. We
will use computational platforms to identify microbial metabolic pathways that correlate with
resistance to viral infections. Microbial consortia that approximate the metabolic networks
detected in resistant hosts will be cultured and administered to gnotobiotic mice or mice that have
been treated with broad-spectrum antibiotics. Although experimental studies have demonstrated
a role for the intestinal microbiota in systemic anti-viral defense the bacterial species mediating
resistance have yet to be defined. Our studies will identify specific bacterial taxa that are
associated with resistance to viral infections that occur following allo-HCT. These studies will
facilitate the identification of mechanisms of anti-viral resistance and may provide approaches to
reduce the incidence of severe viral infections following allo-HCT.

## Key facts

- **NIH application ID:** 10442487
- **Project number:** 5P01CA023766-42
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Eric G. Pamer
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,021
- **Award type:** 5
- **Project period:** 1997-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442487

## Citation

> US National Institutes of Health, RePORTER application 10442487, Project 1: Microbiota-mediated defense against viral infection following SCT (5P01CA023766-42). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10442487. Licensed CC0.

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