Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors
| Autor: | Diane Thibeault, Louise Pilote, Daniel Lamarre, G Croteau, Louise Doyon, F Poulin |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_treatment
Molecular Sequence Data Immunology Drug Resistance Gene Products gag Substrate analog Biology Cleavage (embryo) Antiviral Agents Microbiology chemistry.chemical_compound HIV Protease Virology medicine Humans HIV Protease Inhibitor Amino Acid Sequence Peptide sequence Protease Base Sequence HIV Protease Inhibitors Molecular biology In vitro Reverse transcriptase NS2-3 protease chemistry Insect Science Mutation HIV-1 Research Article |
| Zdroj: | Journal of Virology. 70:3763-3769 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Protease inhibitors are potent antiviral agents against human immunodeficiency virus type 1. As with reverse transcriptase inhibitors, however, resistance to protease inhibitors can develop and is attributed to the appearance of mutations in the protease gene. With the substrate analog protease inhibitors BILA 1906 BS and BILA 2185 BS, 350- to 1,500-fold-resistant variants have been selected in vitro and were found not only to contain mutations in the protease gene but also to contain mutations in Gag precursor p1/p6 and/or NC (p7)/p1 cleavage sites. Mutations in cleavage sites give rise to better peptide substrates for the protease in vitro and to improved processing of p15 precursors in drug-resistant clones. Importantly, removal of cleavage site mutations in resistant clones leads to a decrease or even an absence of viral growth, confirming their role in viral fitness. Therefore, these second-locus mutations indicate that cleavage of p15 is a rate-limiting step in polyprotein processing in highly resistant viruses. The functional constraint of p15 processing also suggests that additional selective pressure could further compromise viral fitness and maintain the benefits of antiviral therapies. |
| Databáze: | OpenAIRE |
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