# Interactions between trichomonasviruses, their parasite host, and the human superhost

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2024 · $15,727

## Abstract

PROJECT SUMMARY
Trichomonas vaginalis viruses (TVVs) are double stranded RNA viruses that persist in the obligate human
parasite Trichomonas vaginalis (Tvag). Tvag is the causative agent of the human disease trichomoniasis, the
most common nonviral sexually transmitted infection worldwide. Infection with TVV-containing parasites is
thought to increase the severity of this disease and its complications by increasing the pro-inflammatory
response by the human superhost. There are five known species in genus Trichomonasvirus (TVV1, TVV2,
TVV3, TVV4, and TVV5), but most experiments to date have been performed using purified TVV1 virions or
TVV1-containing isolates, due in part to the greater availability of Tvag isolates singly infected with TVV1. TVVs
do not have an extracellular lifecycle and instead are transmitted vertically as the parasite divides. Further,
multiple TVV species can coinfect a singular trichomonad. Thus, studying the effect of TVVs on the parasite and
the human superhost has been difficult, as uninfected trichomonads cannot be infected to create isogenic TVV+
vs. TVV- strains. Using the nucleoside analog 2’-C-methylcytidine (2CMC), which has been recently reported to
clear trichomonads of TVV-infection, we have generated isogenic pairs of cured and uncured strains generated
from the same parent isolate. With these isogenic pairs, we propose to test our hypothesis that T. vaginalis
maintains a persistent viral infection, which confers a fitness advantage to the protozoan and increases
virulence to the human superhost. Thus far, we have performed high throughput RNA-sequencing with one
such isogenic pair to measure differential gene expression. In doing so, we have identified several candidate
genes that may be involved in limiting viral replication to tolerable levels in order to maintain long-term viral
persistence. These differentially expressed genes have largely not been characterized, but some encode factors
with homology to known RNA exonucleases and helicases, which we hypothesize might be involved in limiting
viral replication. In Aim 1 of this project, we propose to further validate these results in additional isogenic pairs
in order to define factors Tvag uses to maintain a stable trichomonasvirus infection. In Aim 2, we propose to
determine impacts of TVV infection on Tvag proliferation, morphology, and adherence to human cells. We
hypothesize that TVVs will increase parasite survival and attachment, providing an evolutionary explanation for
long-term TVV persistence. Finally, in Aim 3, we propose to compare responses of human cells to infection with
TVV+ and TVV- trichomonads across TVV species. We anticipate that TVV+ Tvag strains, regardless of virus
species, will elicit stronger inflammatory responses than TVV- strains. Through this work, we hope to uncover
valuable information about an important human pathogen and an intriguing model system to study virus–host
interactions.

## Key facts

- **NIH application ID:** 10893939
- **Project number:** 5F31AI176739-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Carrie Ann Hetzel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $15,727
- **Award type:** 5
- **Project period:** 2023-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893939

## Citation

> US National Institutes of Health, RePORTER application 10893939, Interactions between trichomonasviruses, their parasite host, and the human superhost (5F31AI176739-02). Retrieved via AI Analytics 2026-08-01 from https://api.ai-analytics.org/grant/nih/10893939. Licensed CC0.

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