Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations.
Human immunodeficiency virus type 1 subtype C isolates belong to one of the most prevalent strains circulating worldwide and are responsible for the majority of new infections in the sub-Saharan region and other highly populated areas of the globe. In this work, the impact of drug-resistance mutations in the protease gene of subtype C viruses was analysed and compared with that of subtype B counterparts. A series of recombinant subtype C and B viruses was constructed carrying indinavir (IDV)-resistance mutations (M46V, I54V, V82A and L90M) and their susceptibility to six FDA-approved protease inhibitor compounds (amprenavir, indinavir, lopinavir, ritonavir, saquinavir and nelfinavir) was determined. A different impact of these mutations was found when nelfinavir and lopinavir were tested. The IDV drug-resistance mutations in the subtype C protease backbone were retained for a long period in culture without selective pressure when compared with those in subtype B counterparts in washout experiments.
Gonzalez
Luis M F
LMF
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Aguiar
Renato S
RS
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Afonso
Adriana
A
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Brindeiro
Patricia A
PA
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Arruda
Mônica B
MB
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Soares
Marcelo A
MA
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Brindeiro
Rodrigo M
RM
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
Tanuri
Amílcar
A
Laboratório de Virologia Molecular, Instituto de Biologia, Universidade Federal do Rio de Janeiro, CCS, Bloco A, Cidade Universitária, Ilha do Fundão, 21944-970 Rio de Janeiro, RJ, Brazil.
D024882:Drug Resistance, Viral / Q000235:genetics; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D019469:Indinavir / Q000494:pharmacology*; D061466:Lopinavir; D008826:Microbial Sensitivity Tests; D009154:Mutation; D019888:Nelfinavir / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D013045:Species Specificity; D014779:Virus Replication
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019469:Indinavir; D016333:HIV Protease; D019888:Nelfinavir