Drug-associated changes in amino acid residues in Gag p2, p7NC, and p6Gag/p6Pol in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response
| Autor: | Joshua C. Bunger, Isabel Munoz, Maureen M. Goodenow, Stephanie L. Rose, Roxana M. Coman, Patricia O. O'Brien, Sarah K. Ho, John W. Sleasman, Ben M. Dunn |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_treatment
viruses Molecular Sequence Data Biology Virus Replication gag Gene Products Human Immunodeficiency Virus Virus Article Protease Pi resistance law.invention Cell Line 03 medical and health sciences HIV Protease law Virology Drug Resistance Viral Fitness medicine HIV Protease Inhibitor Humans Amino Acid Sequence Gene Peptide sequence 030304 developmental biology Genetics Recombination Genetic 0303 health sciences Protease 030306 microbiology HIV Protease Inhibitors Phenotype 3. Good health Viral replication Amino Acid Substitution Recombinant DNA HIV-1 |
| Zdroj: | Virology. 378(2):272-281 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2008.05.029 |
| Popis: | Regions of HIV-1 gag between p2 and p6(Gag)/p6(Pol), in addition to protease (PR), develop genetic diversity in HIV-1 infected individuals who fail to suppress virus replication by combination protease inhibitor (PI) therapy. To elucidate functional consequences for viral replication and PI susceptibility by changes in Gag that evolve in vivo during PI therapy, a panel of recombinant viruses was constructed. Residues in Gag p2/p7(NC) cleavage site and p7(NC), combined with residues in the flap of PR, defined novel fitness determinants that restored replicative capacity to the posttherapy virus. Multiple determinants in Gag have a dominant effect on PR phenotype and increase susceptibility to inhibitors of drug-resistant or drug-sensitive PR genes. Gag determinants of drug sensitivity and replication alter the fitness landscape of the virus, and viral replicative capacity can be independent of drug sensitivity. The functional linkage between Gag and PR provides targets for novel therapeutics to inhibit drug-resistant viruses. |
| Databáze: | OpenAIRE |
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