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Updated: Jun 4, 2026
Identifying Caspases and their Motifs that Cleave Proteins During Influenza A Virus Infection
Published on: July 21, 2022
Nuclear envelope disruption involving host caspases plays a role in the parvovirus replication cycle
Sarah Cohen1, Alexandra K Marr, Pierre Garcin
1Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4.
Abstract:
Parvoviruses are small, nonenveloped, single-stranded DNA viruses which replicate in the nucleus of the host cell. We have previously found that early during infection the parvovirus minute virus of mice (MVM) causes small, transient disruptions of the nuclear envelope (NE). We have now investigated the mechanism used by MVM to disrupt the NE. Here we show that the viral phospholipase A2, the only known enzymatic domain on the parvovirus capsid, is not involved in causing NE disruption. Instead, the virus utilizes host cell caspases, which are proteases involved in causing NE breakdown during apoptosis, to facilitate these nuclear membrane disruptions. Studies with pharmacological inhibitors indicate that caspase-3 in particular is involved. A caspase-3 inhibitor prevents nuclear lamin cleavage and NE disruption in MVM-infected mouse fibroblast cells and reduces nuclear entry of MVM capsids and viral gene expression. Caspase-3 is, however, not activated above basal levels in MVM-infected cells, and other aspects of apoptosis are not triggered during early MVM infection. Instead, basally active caspase-3 is relocalized to the nuclei of infected cells. We propose that NE disruption involving caspases plays a role in (i) parvovirus entry into the nucleus and (ii) alteration of the compartmentalization of host proteins in a way that is favorable for the virus.
Insights
Minute virus of mice (MVM) disrupts the nuclear envelope using host cell caspases, not viral enzymes. This process aids viral nuclear entry and gene expression.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Parvoviruses, including minute virus of mice (MVM), are small, single-stranded DNA viruses that replicate in the host cell nucleus.
- MVM infection is known to cause transient disruptions in the nuclear envelope (NE) early in the infection cycle.
Purpose of the Study:
- To elucidate the mechanism by which MVM disrupts the nuclear envelope.
- To determine the role of viral phospholipase A2 and host cell caspases in MVM-induced NE disruption.
Main Methods:
- Utilized pharmacological inhibitors targeting caspases.
- Investigated nuclear lamin cleavage and NE integrity in MVM-infected mouse fibroblast cells.
- Assessed MVM capsid nuclear entry and viral gene expression.
Main Results:
- The viral phospholipase A2 is not responsible for NE disruption.
- Host cell caspases, particularly caspase-3, are utilized by MVM to disrupt the NE.
- Inhibition of caspase-3 prevented nuclear lamin cleavage and NE disruption.
- Caspase-3 inhibition reduced MVM capsid nuclear entry and viral gene expression.
- Caspase-3 was not activated above basal levels, and apoptosis was not triggered; instead, basally active caspase-3 relocalized to the nucleus.
Conclusions:
- MVM disrupts the nuclear envelope by hijacking the host cell's caspase machinery, specifically caspase-3.
- This caspase-mediated NE disruption facilitates MVM nuclear entry and alters host protein compartmentalization to favor viral replication.
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