Immune perturbation following SHIV infection is greater in newborn macaques than in infants
Mariya B. Shapiro, Tracy Ordonez, Shilpi Pandey, Eisa Mahyari, Kosiso Onwuzu, Jason Reed, Heather Sidener, Jeremy Smedley, Lois M. Colgin, Amanda Johnson, Anne D. Lewis, Benjamin Bimber, Jonah B. Sacha, Ann J. Hessell, Nancy L. Haigwood
Mariya B. Shapiro, Tracy Ordonez, Shilpi Pandey, Eisa Mahyari, Kosiso Onwuzu, Jason Reed, Heather Sidener, Jeremy Smedley, Lois M. Colgin, Amanda Johnson, Anne D. Lewis, Benjamin Bimber, Jonah B. Sacha, Ann J. Hessell, Nancy L. Haigwood
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Research Article AIDS/HIV Immunology

Immune perturbation following SHIV infection is greater in newborn macaques than in infants

Abstract

Transmission of HIV-1 to newborns and infants remains high, with 130,000 new infections in 2022 in resource-limited settings. Half of HIV-infected newborns, if untreated, progress to disease and death within 2 years. While immunologic immaturity likely promotes pathogenesis and poor viral control, little is known about immune damage in newborns and infants. Here we examined pathologic, virologic, and immunologic outcomes in rhesus macaques exposed to pathogenic simian-human immunodeficiency virus (SHIV) at 1–2 weeks, defined as newborns, or at 4 months of age, considered infants. Kinetics of plasma viremia and lymph node seeding DNA were indistinguishable in newborns and infants, but levels of viral DNA in gut and lymphoid tissues 6–10 weeks after infection were significantly higher in newborns versus either infant or adult macaques. Two of 6 newborns with the highest viral seeding required euthanasia at 25 days. We observed age-dependent alterations in leukocyte subsets and gene expression. Compared with infants, newborns had stronger skewing of monocytes and CD8+ T cells toward differentiated subsets and little evidence of type I interferon responses by transcriptomic analyses. Thus, SHIV infection reveals distinct immunological alterations in newborn and infant macaques. These studies lay the groundwork for understanding how immune maturation affects pathogenesis in pediatric HIV-1 infection.

Authors

Mariya B. Shapiro, Tracy Ordonez, Shilpi Pandey, Eisa Mahyari, Kosiso Onwuzu, Jason Reed, Heather Sidener, Jeremy Smedley, Lois M. Colgin, Amanda Johnson, Anne D. Lewis, Benjamin Bimber, Jonah B. Sacha, Ann J. Hessell, Nancy L. Haigwood

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Figure 7

Between-group differences in leukocyte counts and phenotypes during SHIV infection in early life.

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Between-group differences in leukocyte counts and phenotypes during SHIV...
(A) For each of 42 parameters measured by flow cytometry, AUC during the first 6 weeks of the study was computed for each group. Groups were compared by 1 t test per AUC comparison (total 2-tailed t tests: 42); P values were adjusted for multiple comparisons by the FDR approach. (B) AUC during the first 6 weeks of SHIV infection was computed for each group, using 1 t test per AUC comparison (total 2-tailed t tests: 42); P values were adjusted for multiple comparisons by the FDR approach. Differences were determined using the 2-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, q = 0.05. Each parameter was analyzed individually, without assuming a consistent SD. Differences are denoted by colored symbols and corresponding labels. In each plot, the horizontal line indicates the –log10-transformed threshold of significance at the q = 0.05 level. Statistically significantly different cell types in spleen and mesenteric LNs collected at necropsy include (C) percentage CD8+ effector memory in the spleen, (D) percentage CD8+ naive in the mesenteric LNs, and (E) percentage NKT cells in the spleen. P values are shown on each graph. Symbols identify animals as defined in Figure 2.