Immunology Laboratory, Vaccine Research Center.
Tissue Analysis Core, Vaccine Research Center.
J Clin Invest. 2021 Sep 1;131(17). doi: 10.1172/JCI151632.
Primary HIV-1 infection can be classified into six Fiebig stages based on virological and serological laboratory testing, whereas simian-HIV (SHIV) infection in nonhuman primates (NHPs) is defined in time post-infection, making it difficult to extrapolate NHP experiments to the clinics. We identified and extensively characterized the Fiebig-equivalent stages in NHPs challenged intrarectally or intravenously with SHIVAD8-EO. During the first month post-challenge, intrarectally challenged monkeys were up to 1 week delayed in progression through stages. However, regardless of the challenge route, stages I-II predominated before, and stages V-VI predominated after, peak viremia. Decrease in lymph node (LN) CD4+ T cell frequency and rise in CD8+ T cells occurred at stage V. LN virus-specific CD8+ T cell responses, dominated by degranulation and TNF, were first detected at stage V and increased at stage VI. A similar late elevation in follicular CXCR5+ CD8+ T cells occurred, consistent with higher plasma CXCL13 levels at these stages. LN SHIVAD8-EO RNA+ cells were present at stage II, but appeared to decline at stage VI when virions accumulated in follicles. Fiebig-equivalent staging of SHIVAD8-EO infection revealed concordance of immunological events between intrarectal and intravenous infection despite different infection progressions, and can inform comparisons of NHP studies with clinical data.
原发性 HIV-1 感染可根据病毒学和血清学实验室检测分为六期 Fiebig 分期，而灵长类动物 HIV（SHIV）感染在非人类灵长类动物（NHP）中的定义是基于感染后的时间，这使得难以将 NHP 实验外推到临床。我们鉴定并广泛描述了经直肠或静脉内接种 SHIVAD8-EO 的 NHP 中的 Fiebig 等效分期。在挑战后第一个月内，经直肠挑战的猴子在通过分期的过程中延迟了长达 1 周。然而，无论挑战途径如何，在峰值病毒血症之前，I-II 期占主导地位，而在峰值病毒血症之后，V-VI 期占主导地位。淋巴结（LN）CD4+T 细胞频率下降和 CD8+T 细胞上升发生在 V 期。在 V 期首次检测到以脱颗粒和 TNF 为主导的 LN 病毒特异性 CD8+T 细胞反应，并在 VI 期增加。类似地，滤泡 CXCR5+CD8+T 细胞在晚期升高，与这些阶段的血浆 CXCL13 水平升高一致。在 II 期存在 LN SHIVAD8-EO RNA+细胞，但当病毒粒子在滤泡中积累时，似乎在 VI 期下降。SHIVAD8-EO 感染的 Fiebig 等效分期显示，尽管感染进展不同，但直肠内和静脉内感染之间的免疫事件具有一致性，并且可以为将 NHP 研究与临床数据进行比较提供信息。
