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Published on: January 31, 2018
Protoparvovirus Interactions with the Cellular DNA Damage Response
Kinjal Majumder1, Igor Etingov2, David J Pintel3
1Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Bond Life Sciences Center, Columbia, MO 65211, USA. km3k5@missouri.edu.
Abstract:
Protoparvoviruses are simple single-stranded DNA viruses that infect many animal species. The protoparvovirus minute virus of mice (MVM) infects murine and transformed human cells provoking a sustained DNA damage response (DDR). This DDR is dependent on signaling by the ATM kinase and leads to a prolonged pre-mitotic cell cycle block that features the inactivation of ATR-kinase mediated signaling, proteasome-targeted degradation of p21, and inhibition of cyclin B1 expression. This review explores how protoparvoviruses, and specifically MVM, co-opt the common mechanisms regulating the DDR and cell cycle progression in order to prepare the host nuclear environment for productive infection.
Insights
Protoparvoviruses, like the minute virus of mice (MVM), trigger a DNA damage response (DDR) in host cells. This response manipulates cell cycle progression to create an environment favorable for viral replication.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Protoparvoviruses are single-stranded DNA viruses with a broad host range.
- Minute virus of mice (MVM) infection induces a sustained DNA damage response (DDR) in host cells.
- The MVM-induced DDR involves ATM kinase signaling and impacts cell cycle regulators.
Purpose of the Study:
- To review how protoparvoviruses, particularly MVM, exploit host cell machinery.
- To elucidate the mechanisms by which MVM manipulates the DNA damage response (DDR) and cell cycle.
- To understand how MVM optimizes the host nuclear environment for viral replication.
Main Methods:
- Literature review of studies on protoparvovirus infection and host cell responses.
- Analysis of molecular pathways involved in DNA damage response (DDR) and cell cycle regulation.
- Examination of viral strategies for manipulating host cell processes.
Main Results:
- MVM infection elicits a DDR dependent on ATM kinase.
- This DDR results in a cell cycle block prior to mitosis.
- Key events include ATR-kinase signaling inactivation, p21 degradation, and inhibited cyclin B1 expression.
Conclusions:
- Protoparvoviruses co-opt host DDR and cell cycle mechanisms for their benefit.
- Viral manipulation of these pathways facilitates productive infection.
- Understanding these interactions offers insights into viral pathogenesis and host-pathogen dynamics.
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