Bovine Leukemia Virus Protease: Comparison with Human T-lymphotropic Virus and Human Immunodeficiency Virus Proteases.
From: Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Hungary.
The Journal of general virology
- Publish Date: Jul 2007
- ISSN: 0022-1317
- Volume: 88
- Issue: Pt 7
- Pages: 2052-63
- Medium: Print
- Language: English
- Citation (JAMA): Sperka Tamás, Miklóssy Gabriella, Tie Yunfeng, et al. Bovine Leukemia Virus Protease: Comparison with Human T-lymphotropic Virus and Human Immunodeficiency Virus Proteases.. J. Gen. Virol. Jul 2007;88:2052-63
Abstract
Bovine leukemia virus (BLV) is a valuable model system for understanding human T-lymphotropic virus 1 (HTLV-1); the availability of an infectious BLV clone, together with animal-model systems, will help to explore anti-HTLV-1 strategies. Nevertheless, the specificity and inhibitor sensitivity of the BLV protease (PR) have not been characterized in detail. To facilitate such studies, a molecular model for the enzyme was built. The specificity of the BLV PR was studied with a set of oligopeptides representing naturally occurring cleavage sites in various retroviruses. Unlike HTLV-1 PR, but similar to the human immunodeficiency virus 1 (HIV-1) enzyme, BLV PR was able to hydrolyse the majority of the peptides, mostly at the same position as did their respective host PRs, indicating a broad specificity. When amino acid residues of the BLV PR substrate-binding sites were replaced by equivalent ones of the HIV-1 PR, many substitutions resulted in inactive protein, indicating a great sensitivity to mutations, as observed previously for the HTLV-1 PR. The specificity of the enzyme was studied further by using a series of peptides containing amino acid substitutions in a sequence representing a naturally occurring HTLV-1 PR cleavage site. Also, inhibitors of HIV-1 PR, HTLV-1 PR and other retroviral proteases were tested on the BLV PR. Interestingly, the BLV PR was more susceptible than the HTLV-1 PR to the inhibitors tested. Therefore, despite the specificity differences, in terms of mutation intolerance and inhibitor susceptibility of the PR, BLV and the corresponding animal-model systems may provide good models for testing of PR inhibitors that target HTLV-1.
Mesh Headings (Keywords): Amino Acid Sequence, Amino Acid Substitution, Animals, Binding Sites, Cattle, HIV-1, Human T-lymphotropic virus 1, Humans, Leukemia Virus, Bovine, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Peptide Fragments, Peptide Hydrolases, Protease Inhibitors, Sequence Homology, Amino Acid, Species Specificity, Substrate Specificity, Viral Proteins
Check for Full Text / PubMed Unique Identifier (PMID): 17554040
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