# Roles of Pteropine Bat and Human TRIMs in Regulating Henipavirus Infection

> **NIH NIH F31** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $34,754

## Abstract

Project Summary
Bat species are the natural hosts of several emerging and re-emerging viruses including henipaviruses (HNVs).
Although infection with these viruses causes high case fatality rates in humans, bats appear tolerant. Old World
fruit bats in the family Pteropodidae are the natural reservoirs of HNVs, including Henda (HeV) and Nipah (NiV).
HNV-pteropine bat ecological interactions are well-studied, but the mechanisms underlying the limited
immunopathology in pteropine bats following HNV infection are unknown.
During HNV infection in humans, the antiviral type I interferon (IFN-I) pathways are suppressed in part through
the antagonism of tripartite motif proteins (TRIMs). TRIMs are involved in modulating antiviral immune responses
including IFN-I production and signaling pathways. Some members of the TRIM E3 ubiquitin ligase family
stimulate the IFN-I and pro-inflammatory antiviral pathways to promote viral clearance while others antagonize
these pathways to limit immune-associated pathology. We have generated preliminary data that demonstrates
NiV activates the IFN-I signaling pathway human cells late in infection, but IFN-I signaling remains antagonized
efficiently in bat cells throughout the duration of infection. Based on this observation, we predict that bats have
evolved to express a TRIM in response to NiV infection that negatively regulates the cytoplasmic RNA recognition
pathway to prevent the cytopathic effects of innate immune signaling. Previously, we described the role of NiV
matrix protein (NiV-M) in the degradation of human TRIM6, which inhibits TRIM6-mediated activation of IKKε-
dependent IFN-I production and signaling. We found that bat TRIM6 interacts with NiV-M, but bat TRIM6 resists
NiV-M mediated degradation. Due to this species-specific difference, we are interested in identifying the
mechanisms that confer degradation resistance to bat TRIM6 and understanding the roles of TRIM6 during NiV
infection.
In this proposal, we hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in
bat, but not human, cells that promotes tolerance, and that species-specific differences in NiV-M-mediated
TRIM6 degradation influences the course of infection. We will interrogate our hypothesis through two specific
aims: (1) to identify pteropine and human TRIM orthologs differentially expressed after NiV infection and
determine their roles in innate immune regulation and (2) To elucidate the mechanistic roles of human and bat
TRIM6 in regulating NiV infection. Overall, the results of the proposed study will promote our understanding of
the molecular regulation of pteropine bat IFN-I pathways and potentially identify factors that facilitate bats’
tolerance to HNVs. Elucidating the mechanisms that promote tolerance to HNV may serve as a basis for the
development of human therapeutics.

## Key facts

- **NIH application ID:** 10233248
- **Project number:** 1F31AI152422-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Sarah van Tol
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,754
- **Award type:** 1
- **Project period:** 2021-03-15 → 2023-03-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233248

## Citation

> US National Institutes of Health, RePORTER application 10233248, Roles of Pteropine Bat and Human TRIMs in Regulating Henipavirus Infection (1F31AI152422-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10233248. Licensed CC0.

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