CHARACTERIZATION OF MOLECULARLY CLONED SIMIAN HUMAN IMMUNODEFICIENCY VIRUSES

猴免疫缺陷病毒(SIV)感染的研究 亚洲猕猴提供了许多关于糖尿病发病机制的见解。 人类免疫缺陷病毒1型(HIV-1)感染者中的艾滋病。 SIVmac和HIV-1包膜糖蛋白的差异， 然而，限制了SIVmac模型用于研究HIV-1的实用性 致病性的包膜糖蛋白决定因素和检测用 针对HIV-1包膜糖蛋白的疫苗策略。 猴-人嵌合免疫缺陷病毒的体内传代 (SHIV-89.6)表达HIV-1 Tat、rev、VPU和env基因 致病病毒(SIV-89.6P)诱导快速的CD4+淋巴细胞耗竭 和恒河猴的艾滋病样疾病(J Virol 70：6922-6928,1996)。 由SHV-89.6P的一些前病毒克隆产生的病毒引起了 并在很高比例的CD_4~+淋巴细胞显著下降 给猕猴接种疫苗。核苷酸变化可能是导致 SIV-89.6P毒力增强仅限于env、tat或long 末端重复序列，大部分观察到的环境变化。 Env的核苷酸变化改变了gp120和gp41的12个氨基酸。 外部结构域，以及env中140个碱基的缺失导致 SIVmac gp41糖蛋白羧基末端的取代 针对HIV-1 gp41糖蛋白。是否可以使用 致病性前病毒克隆应有助于解剖 新城疫病毒89.6P毒力的分子决定因素及毒力评价 HIV-1疫苗战略。

The study of simian immunodeficiency virus (SIV) infection in Asian macaques has provided numerous insights into the pathogenesis of AIDS in human immunodeficiency virus type 1 (HIV-1)-infected humans. The divergence of the envelope glycoproteins of SIVmac and HIV-1, however, limit the utility of the SIVmac model for studying HIV-1 envelope glycoprotein determinants of pathogenicity, and for testing vaccine strategies directed against the HIV-1 envelope glycoproteins. In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6) expressing HIV-1 tat, rev, vpu and env genes generated pathogenic virus (SHIV-89.6P) inducing rapid CD4+ lymphocyte depletion and AIDS-like illness in rhesus monkeys (J Virol 70:6922-6928, 1996). Virus generated from some proviral clones of SHIV-89.6P caused a rapid and profound decline of CD4+ lymphocytes in a high percentage of inoculated macaques. Nucleotide changes potentially responsible for increased virulence of SHIV-89.6P were limited to the env, tat or long terminal repeat sequences, with most of the observed changes in env. Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140 bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral clones should facilitate dissection of the molecular determinant of SHIV-89.6P virulence and the evaluation of HIV-1 vaccine strategies.