Concordance of immunological events between intrarectal and intravenous SHIVAD8-EO infection when assessed by Fiebig-equivalent staging
Joana Dias, … , John R. Mascola, Richard A. Koup
Joana Dias, … , John R. Mascola, Richard A. Koup
Published September 1, 2021
Citation Information: J Clin Invest. 2021;131(17):e151632. https://doi.org/10.1172/JCI151632.
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Research Article AIDS/HIV Immunology

Concordance of immunological events between intrarectal and intravenous SHIVAD8-EO infection when assessed by Fiebig-equivalent staging

Abstract

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.

Authors

Joana Dias, Giulia Fabozzi, Kylie March, Mangaiarkarasi Asokan, Cassandra G. Almasri, Jonathan Fintzi, Wanwisa Promsote, Yoshiaki Nishimura, John-Paul Todd, Jeffrey D. Lifson, Malcolm A. Martin, Lucio Gama, Constantinos Petrovas, Amarendra Pegu, John R. Mascola, Richard A. Koup

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Figure 4

Immune cell distribution in the LNs throughout the Fiebig-equivalent stages of SHIVAD8-EO infection.

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Immune cell distribution in the LNs throughout the Fiebig-equivalent sta...
(A) Average distribution of LN samples for flow cytometry immunophenotyping analysis (shown in Figure 4) and CD8+ T cell functional analysis (shown in Figure 5) across the Fiebig-equivalent stages of SHIVAD8-EO infection (the numbers in parentheses indicate the number of samples available for the functional analysis shown in Figure 5 when the sample number was different from that for the immunophenotyping analysis shown in Figure 4). (B–D) Frequency of monocytes, NK cells, B cells, and T cells (B), CD4+ (left) and CD8+ (right) T cells (C), and GC Tfh (left) and fCD8+ T cells (right) (D) at the different stages of SHIVAD8-EO infection. Graphs show the mean (A), the mean ± SEM (B), and the mean ± SEM and individual data points (C and D). The Kruskal-Wallis test followed by Dunn’s multiple-comparison test was used to detect significant differences between the pre-challenge phase, Fiebig-equivalent stages II, V, and VI of SHIVAD8-EO infection (B–D). *P < 0.05; **P < 0.01. ecl., eclipse; fCD8+, follicular CD8+; GC, germinal center; Tfh, T follicular helper.