# Murine model for Torque teno viruses - Resubmission - 1

> **NIH NIH R21** · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · 2020 · $190,000

## Abstract

Abstract
Torque teno viruses (TTVs) are one of the most common constituents of the human virome and almost all
metagenomics studies report TTVs as the most abundant viruses in human blood. TTVs are non-enveloped,
with a capsid diameter of ~30nm and have a single strand, negative sense DNA genome. These viruses infect
humans and several animal species, but despite their high-genetic diversity, all TTVs share a highly conserved
100-130 nt long untranslated region. Phylogenetic analysis of TTV variants found in different host species
suggest their species specificity, but experimental infection studies to rule out cross-species transmission are
not reported, except in chimpanzees. Despite being a common and persistent virus infection of humans, the
biological characteristics and health relevance of TTVs remain largely unknown due to the lack of an informative
animal model or cell culture system. A tractable and genetically amenable model for TTVs infection can shed
new light on the biological properties and health relevance of these common viruses. Our efforts to infect
immunocompetent and immunocompromised mice with human TTVs were unsuccessful. Animal homologs of
human viruses can provide informative surrogate models to study virus infection, immunity and pathogenesis.
Some examples are Simian Immunodeficiency virus, murine cytomegaloviruses, murine norovirus, woodchuck
hepatitis B virus and rat hepatitis C-like virus. We therefore looked for TTVs in feral mice, rats and other rodent
species. Interestingly, no TTVs were found in feral mice (Mus musculus), but several genotypes of TTVs were
found in feral rats of two different, yet closely related species, Rattus norvegicus and Rattus rattus. Here, we
propose to use these feral rat viruses to develop tractable murine models for TTVs infection and propose two
specific aims for this exploratory project. Aim-1 is to study the basic biological properties of rat TTVs in inbred
and outbred laboratory rats. We will study the nature of their infection (acute or chronic), transmission, tissue
tropism and species specificity. Aim-2 is to study the health relevance of TTV infection by characterizing antiviral
host responses. We will analyze functional virus-specific T-cell responses, cytokines and will also use RNA-seq
analysis of virus-infected tissues to study the host transcriptional changes induced by TTV infection. A well-
characterized, tractable and genetically amenable murine model for TTV, one of the most common human virus
infections, will help aid our understanding of their biological properties and health relevance.

## Key facts

- **NIH application ID:** 9937659
- **Project number:** 5R21AI142433-02
- **Recipient organization:** RESEARCH INST NATIONWIDE CHILDREN'S HOSP
- **Principal Investigator:** Amit Kapoor
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $190,000
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937659

## Citation

> US National Institutes of Health, RePORTER application 9937659, Murine model for Torque teno viruses - Resubmission - 1 (5R21AI142433-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9937659. Licensed CC0.

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