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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.
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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