Pal Ranajit, Galmin Lindsey, Pereira Lara E, Li Bin, Zhang Jining, Li Daniel, Francis Jesse, McNicholl Janet M, Weiss Deborah E, Smith James M
Advanced BioScience Laboratories Inc., Rockville, MD 20850, USA.
Virology. 2012 Oct 10;432(1):173-83. doi: 10.1016/j.virol.2012.05.034. Epub 2012 Jul 5.
Simian-human immunodeficiency virus encoding both reverse transcriptase (RT) and envelope genes of HIV-1 (RT Env SHIV) is important for evaluating biomedical prevention modalities for HIV/AIDS. We describe virological characterization of a clade B RT Env SHIV following infection of macaques via multiple routes. In vivo passage of the RT Env SHIV through Indian rhesus macaque enhanced infectivity. Expanded virus had minimal envelope heterogeneity and was inhibited by NNRTIs and CCR5 antagonists. Infection of macaques with RT Env SHIV via mucosal or intravenous routes resulted in stable infection accompanied by peak plasma viremia of approximately 5×10(6) copies/ml that was controlled beyond set point. Molecular homogeneity of the virus was maintained following in vivo passage. Inhibition of RT Env SHIV by RT and entry inhibitors and ease of in vivo transmission make it a useful model for testing the efficacy of combinations of entry and RT inhibitors in nonhuman primates.
编码HIV-1逆转录酶(RT)和包膜基因的猿猴-人类免疫缺陷病毒(RT Env SHIV)对于评估HIV/AIDS的生物医学预防方法很重要。我们描述了通过多种途径感染猕猴后B亚型RT Env SHIV的病毒学特征。RT Env SHIV在印度恒河猴体内传代增强了感染性。传代后的病毒包膜异质性最小,并被非核苷类逆转录酶抑制剂(NNRTIs)和CCR5拮抗剂抑制。通过黏膜或静脉途径用RT Env SHIV感染猕猴会导致稳定感染,伴有约5×10⁶拷贝/毫升的血浆病毒血症峰值,该峰值在设定点之后得到控制。病毒在体内传代后保持了分子同质性。RT Env SHIV对RT和进入抑制剂的敏感性以及易于在体内传播,使其成为在非人灵长类动物中测试进入抑制剂和RT抑制剂联合疗效的有用模型。