Bogers W M, Koornstra W H, Dubbes R H, ten Haaft P J, Verstrepen B E, Jhagjhoorsingh S S, Haaksma A G, Niphuis H, Laman J D, Norley S, Schuitemaker H, Goudsmit J, Hunsmann G, Heeney J L, Wigzell H
Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
J Gen Virol. 1998 Dec;79 ( Pt 12):2895-903. doi: 10.1099/0022-1317-79-12-2895.
The aim of the study was to select, from a panel of candidate European human immunodeficiency virus type 1 (HIV-1) clade B primary virus isolates, one isolate based on replication properties in chimpanzee peripheral blood mononuclear cells (PBMC). Secondly, to evaluate the in vivo kinetics of primary infection of the selected isolate at two different doses in two mature, outbred chimpanzees (Pan troglodytes). Four different low passage, human PBMC-cultured 'primary' HIV-1 isolates with European clade B consensus sequence were compared for their ability to replicate in vitro in chimpanzee versus human PBMC. The isolate which yielded the highest titre and most vigorous cytopathic effect in chimpanzee PBMC was evaluated for coreceptor usage and chosen for evaluation in vivo. Only the HIV-1Han2 isolate replicated in chimpanzee PBMC in vitro at detectable levels. This isolate was demonstrated to utilize CCR4, CCR5 and CXCR4 coreceptors and could be inhibited by beta-chemokines. Infection of chimpanzees was demonstrated by viral RNA and DNA PCR analysis, both in plasma as well as in PBMC and lymph node cells as early as 3 weeks after inoculation. Antibodies developed within 6 weeks and continued to increase to a maximum titre of approximately 12800, thereafter remaining in this range over the follow-up period of 2 years. Compared to cell line-adapted HIV-1 isolates there were slight but no dramatic differences in the kinetics of infection of chimpanzees with this particular primary isolate.
本研究的目的是从一组候选的欧洲1型人类免疫缺陷病毒（HIV-1）B亚型原发性病毒分离株中，基于在黑猩猩外周血单核细胞（PBMC）中的复制特性选择一株分离株。其次，在两只成熟的、远交的黑猩猩（Pan troglodytes）中，评估所选分离株在两种不同剂量下的原发性感染的体内动力学。比较了四种不同的低传代、在人PBMC中培养的具有欧洲B亚型共有序列的“原发性”HIV-1分离株在黑猩猩与人类PBMC中体外复制的能力。在黑猩猩PBMC中产生最高滴度和最强烈细胞病变效应的分离株被评估其共受体使用情况，并被选用于体内评估。只有HIV-1Han2分离株在体外能在黑猩猩PBMC中以可检测水平复制。该分离株被证明利用CCR4、CCR5和CXCR4共受体，并且可被β趋化因子抑制。接种后3周，通过病毒RNA和DNA PCR分析在血浆以及PBMC和淋巴结细胞中均证实了黑猩猩被感染。抗体在6周内产生，并持续增加至最高滴度约12800，此后在2年的随访期内保持在该范围内。与细胞系适应的HIV-1分离株相比，用这种特定的原发性分离株感染黑猩猩的动力学存在轻微但无显著差异。
