Kimata J T, Kuller L, Anderson D B, Dailey P, Overbaugh J
Department of Microbiology, University of Washington, Seattle 98195, USA.
Nat Med. 1999 May;5(5):535-41. doi: 10.1038/8414.
Genetic variants of human and simian immunodeficiency virus (HIV and SIV) that evolve during the course of infection and progression to AIDS are phenotypically and antigenically distinct from their progenitor viruses present at early stages of infection. However, it has been unclear how these late variants, which are typically T-cell tropic, cytopathic and resistant to neutralizing antibodies, influence the development of clinical AIDS. To address this, we infected macaques with cloned SIVs representing prototype variants from early-, intermediate- and late-stage infection having biological characteristics typical of viruses found at similar stages of HIV infection in humans. These studies demonstrate that sequential, phenotypic and antigenic variants represent viruses that have become increasingly fit for replication in the host, and our data support the hypothesis that emerging variants have increased pathogenicity and drive disease progression in SIV and HIV infection.
人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）的基因变体在感染过程中以及发展为艾滋病的进程中不断演变，在表型和抗原性上与其感染早期存在的原始病毒不同。然而，目前尚不清楚这些通常具有T细胞嗜性、细胞病变性且对中和抗体具有抗性的晚期变体如何影响临床艾滋病的发展。为了解决这个问题，我们用克隆的SIV感染猕猴，这些克隆的SIV代表了来自早期、中期和晚期感染的原型变体，具有在人类HIV感染相似阶段发现的病毒的典型生物学特征。这些研究表明，连续的、表型和抗原性变体代表了越来越适合在宿主体内复制的病毒，我们的数据支持这样的假设，即新出现的变体增加了致病性，并推动了SIV和HIV感染中的疾病进展。
