Gonzalez Luis M F, Aguiar Renato S, Afonso Adriana, Brindeiro Patricia A, Arruda Mônica B, Soares Marcelo A, Brindeiro Rodrigo M, Tanuri Amílcar
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.
J Gen Virol. 2006 May;87(Pt 5):1303-1309. doi: 10.1099/vir.0.81517-0.
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.
1型人类免疫缺陷病毒C亚型毒株属于全球传播最广泛的毒株之一，是撒哈拉以南地区及全球其他人口密集地区大多数新感染病例的致病源。在本研究中，分析了C亚型病毒蛋白酶基因中耐药性突变的影响，并与B亚型病毒进行了比较。构建了一系列携带茚地那韦（IDV）耐药性突变（M46V、I54V、V82A和L90M）的重组C亚型和B亚型病毒，并测定了它们对六种美国食品药品监督管理局（FDA）批准的蛋白酶抑制剂化合物（安普那韦、茚地那韦、洛匹那韦、利托那韦、沙奎那韦和奈非那韦）的敏感性。在测试奈非那韦和洛匹那韦时，发现这些突变产生了不同的影响。在洗脱实验中，与B亚型病毒相比，C亚型蛋白酶主干中的IDV耐药性突变在无选择压力的培养条件下能长时间保留。
