# Analysis of cellular factors limiting productive JC virus infections

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $196,927

## Abstract

Project Summary
JCV and BKV are members of the Polyomavirus family that infect a large portion of the human population.
Under normal conditions both viruses establish a lifelong, asymptomatic, persistent infection in the kidneys,
and are frequently detected in urine and circulating blood without apparent consequences. While in most cases
JCV and BKV are harmless, they can reactivate in immunosuppressed patients, and then induce serious
diseases. However, the outcome from either infection is very different: BKV infection induces an inflammatory
response and tissue damage in the kidney that results in nephropathy and hemorrhagic cystitis, while JCV
reactivation causes fatal neurodegeneration in the brain, but only a few nephropathy cases. The factors
governing the equilibrium between viral productive infection and persistent infection are unknown, as are the
mechanisms controlling the different cellular responses to similar polyomaviruses.
This application focuses on understanding the basis for cellular responses to JCV in a relevant primary human
cell type, renal proximal tubule epithelial cells (RPTE). In contrast with BKV, whose infection induces extensive
cell death around 5 dpi and the release of about 40 infectious particles/cell, JCV establishes a low-level
infection in RPTE, causing minimal cytopathic effects and persisting for at least 3 weeks without inducing a full
productive infection. Inoculation of RPTE with JCV results in induction of the interferon response, which could
prevent viral expansion.
This research will use human primary cells to identify the factors that influence infection outcomes: productive
or persistent. Activation of the interferon response by JCV infection in RPTE will be assessed using both
molecular and functional approaches to identify components of the pathway that are critical for responding to
the virus and for limiting viral infection. Then, single cell transcriptomics will be applied to RPTE to assess the
response of cell subpopulations to infection and to identify genes that play a role in restricting JCV replication.
Finally, a comparison between the responses observed upon infection of RPTE with either BKV or JCV will be
used to identify cellular genes that distinguish abortively versus productively infected cells.
This application seeks to understand the unique responses to JCV in a clinically relevant human primary cell
from the kidneys, the mechanisms that drive those responses and how the same cells respond in a different
fashion to infection with BKV. This research will increase our understanding of principles governing cellular
responses to viral infection, and how these responses influence the outcome of infection.

## Key facts

- **NIH application ID:** 10312804
- **Project number:** 5R21AI151612-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JAMES M PIPAS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,927
- **Award type:** 5
- **Project period:** 2020-12-07 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312804

## Citation

> US National Institutes of Health, RePORTER application 10312804, Analysis of cellular factors limiting productive JC virus infections (5R21AI151612-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10312804. Licensed CC0.

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