# Interaction between parvovirus replication and the cellular DNA-damage response

> **NIH NIH F32** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $47,760

## Abstract

PROJECT SUMMARY
 Viruses, especially DNA viruses, elicit DNA damage responses (DDRs) in infected cells which are
innate, critical barriers that can either impede or facilitate virus replication, and so must be successfully
negotiated for infection to succeed. Replication of the parvovirus minute virus of mice (MVM) induces a
sustained cellular DNA damage response (DDR) which the virus then exploits to enhance its infection in host
cells. The Parvovirinae are small non-enveloped icosahedral viruses that are important pathogens in many
animal species including humans. They are the only known viruses of vertebrates that contain single-stranded
linear DNA genomes, and thus, present novel replicative DNA structures to cells during infection. They rely
extensively on cellular processes for replication. This F32 application proposes a comprehensive and intensive
training program whose scientific objective is to further investigate how MVM exploits the cellular DDR to
prepare the nuclear environment for effective parvovirus takeover, focusing on the following aims:
 Aim 1: Identify where MVM establishes infection and characterize how its proximity to the host-
genome changes temporally. Successful MVM replication leads to the formation of viral replication centers in
the nuclear environment. It is not known where in the nucleus the virus establishes its replication bodies, and
what part of the cellular genome it interacts with. We propose to identify the interactome of MVM replication
bodies using chromosome conformation capture assays and how this association evolves throughout infection.
 Aim 2: Determine how MVM-NS1 aids in the establishment of viral replication centers. The MVM
non-structural protein NS1, essential for viral replication, forms a core component of viral replication centers.
Our preliminary data indicates that NS1 binds to cellular DNA at specific sites, perhaps assisting viral genomes
as they establish replication centers at these cellular sites. Thus, we propose to identify the binding sites of
NS1 throughout the cellular genome, and test the role of NS1 as a mediator of MVM-host interaction
 Aim 3: Determine how cellular DNA damage affects virus localization and replication. MVM
infection elicits a DDR, leading to cell-cycle defects and the generation of cellular DNA breaks. Accumulation of
DDR proteins at cellular sites can serve as hotspots for viral replication to occur. If this is true, engineered DNA
breaks at selected sites would be predicted to recruit viral genomes. We propose to test the recruitment of
MVM to engineered DNA breaks in a cell-line model, how genome recruitment changes temporally with DNA
break induction, and characterize how DDR proteins accumulate over time at these sites.
 This work will add fundamental knowledge into how a small DNA virus negotiates the nuclear
environment to initiate infection, and provide important information concerning how cells respond to the insult
of incoming viral single-stranded D...

## Key facts

- **NIH application ID:** 9823832
- **Project number:** 5F32AI131468-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Kinjal Majumder
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $47,760
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-07-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823832

## Citation

> US National Institutes of Health, RePORTER application 9823832, Interaction between parvovirus replication and the cellular DNA-damage response (5F32AI131468-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9823832. Licensed CC0.

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