# Using human intestinal organoids to evaluate JCV fecal/oral transmission

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2024 · $228,750

## Abstract

Project summary
 JC virus (JCV) is a human polyomavirus which infects most of the human population worldwide during
early childhood with 50-70% of the adult population being seropositive for the virus. JCV is thought to be
transmitted by the oral/fecal route however the primary site of infection has not been identified. Following an
initial infection, JCV transits into the kidneys where it establishes a lifelong infection. For most people this
infection is latent and no new virus particles are detected, however about 8-20% of people have a low-level virus
production leading to the excretion of virus into the urine. For immune-competent individuals these lifelong
infections will be asymptomatic. However, for immune-suppressed patients, these viruses can reactivate leading
to fatal disorders. Upon immunosuppression, JCV will leave the kidney and move to the brain where it will infect
the myelin-producing oligodendrocytes. Infection of the oligodendrocytes will lead to their lytic destruction
causing the fatal disorder Progressive Multifocal Leukoencephalopathy (PML). JCV genomes have been found
in both upper and lower gastrointestinal tissues and in feces suggesting that human intestinal cells can support
JCV infection. While the consensus view is that initial infection of the human population by JCV is by ingestion,
direct evidence of infection of the intestine is lacking. Most importantly, how JCV passes the intestinal epithelial
cell barrier en route to the kidney remains unknown. We plan to fill these gaps in knowledge and study how JCV
infects, replicates, and spreads in human intestinal epithelial cells. Understanding the enteric phase of JCV is of
major significance to understand JCV pathogenesis as it is believed to constitute the entry site from which 70%
of the population becomes infected. In a set of preliminary data using human intestinal organoids, as a surrogate
system to study JCV infection in human primary intestinal cells, we could show that JCV can replicate in human
intestinal cells and produce de novo infectious virus particles. In this proposal, we will build on our preliminary
data and address the cellular tropism of JCV by evaluating the susceptibility of different human intestinal cell
types to JCV infection. Additionally, we will test whether all sections of the gastrointestinal tract (duodenum,
jejunum, ileum, and colon) can support JCV infection. Finally, we will determine how JCV passes the intestinal
epithelial barrier en route to the kidney to establish its chronic infection. We anticipate that this work will provide
us with unique opportunities to identify novel therapeutic to prevent infection/transmission from the intestinal
mucosa. Importantly this work, will constitute the building block for future research that will integrate the natural
gut/kidney axis that is likely to play an important role in JCV infection and pathogenesis.

## Key facts

- **NIH application ID:** 10985264
- **Project number:** 1R21AI180481-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Steeve Boulant
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $228,750
- **Award type:** 1
- **Project period:** 2024-06-03 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985264

## Citation

> US National Institutes of Health, RePORTER application 10985264, Using human intestinal organoids to evaluate JCV fecal/oral transmission (1R21AI180481-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10985264. Licensed CC0.

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