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Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations

Amílcar Tanuri

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

Correspondence
Amílcar Tanuri
atanuri{at}biologia.ufrj.br

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.

Primer sequences are available as supplementary material in JGV Online.

Present address: Global AIDS Program Laboratory Activity, NCHSTP, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road MS A12, Atlanta, GA 30333, USA.

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