RT Journal Article SR Electronic(1) A1 Sperka, Tamás A1 Miklóssy, Gabriella A1 Tie, Yunfeng A1 Bagossi, Péter A1 Zahuczky, Gábor A1 Boross, Péter A1 Matúz, Krisztina A1 Harrison, Robert W. A1 Weber, Irene T. A1 Tözsér, JózsefYR 2007 T1 Bovine leukemia virus protease: comparison with human T-lymphotropic virus and human immunodeficiency virus proteases JF Journal of General Virology, VO 88 IS 7 SP 2052 OP 2063 DO https://doi.org/10.1099/vir.0.82704-0 PB Microbiology Society, SN 1465-2099, AB 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., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82704-0