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Cleavage of vimentin by different retroviral proteases
J Snásel1, R Shoeman, M Horejsí
1Department of Biochemistry, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.
Abstract:
Proteases (PRs) of retroviruses cleave viral polyproteins into their mature structural proteins and replication enzymes. Besides this essential role in the replication cycle of retroviruses, PRs also cleave a variety of host cell proteins. We have analyzed the in vitro cleavage of mouse vimentin by proteases of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), bovine leukemia virus (BLV), Mason-Pfizer monkey virus (M-PMV), myeloblastosis-associated virus (MAV), and two active-site mutants of MAV PR. Retroviral proteases display significant differences in specificity requirements. Here, we show a comparison of substrate specificities of several retroviral proteases on vimentin as a substrate. Vimentin was cleaved by all the proteases at different sites and with different rates. The results show that the physiologically important cellular protein vimentin can be degraded by different retroviral proteases.
Insights
Retroviral proteases, like those from HIV, can degrade the important cellular protein vimentin. Different proteases cleave vimentin at various sites and speeds, revealing distinct substrate specificities.
Area of Science:
- Virology
- Molecular Biology
- Cellular Biology
Background:
- Retroviral proteases (PRs) are essential for viral replication, processing viral polyproteins into functional units.
- Beyond viral substrates, retroviral PRs are known to interact with and cleave host cell proteins.
Purpose of the Study:
- To compare the substrate specificities of various retroviral proteases using mouse vimentin as a model substrate.
- To investigate the in vitro cleavage patterns of vimentin by proteases from HIV-1, HIV-2, BLV, M-PMV, and MAV.
Main Methods:
- In vitro analysis of substrate cleavage.
- Utilized purified proteases from multiple retroviruses (HIV-1, HIV-2, BLV, M-PMV, MAV) and active-site mutants.
- Mouse vimentin served as the substrate to assess protease activity and specificity.
Main Results:
- All tested retroviral proteases, including those from HIV and BLV, were capable of cleaving mouse vimentin.
- Cleavage occurred at distinct sites within the vimentin protein, varying in rate among the different proteases.
- Demonstrated significant differences in substrate specificity among the retroviral proteases tested on vimentin.
Conclusions:
- The cellular protein vimentin is a substrate for a range of retroviral proteases.
- Retroviral proteases exhibit diverse specificities when acting upon host cell proteins like vimentin.
- These findings highlight the potential for retroviral proteases to disrupt host cell functions through protein degradation.