Perivascular macrophages in the neonatal macaque brain undergo massive necroptosis after simian immunodeficiency virus infection

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV‐infected adults. We hypothesize that differences in myeloid cell...

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Published in:	Brain pathology (Zurich, Switzerland) Vol. 30; no. 3; pp. 603 - 613
Main Authors:	Bohannon, Diana G., Wang, Yueying, Reinhart, Colin H., Hattler, Julian B., Luo, Jiangtao, Okhravi, Hamid R., Zhang, Jianshui, Li, Qingsheng, Kuroda, Marcelo J., Kim, Jayoung, Kim, Woong‐Ki
Format:	Journal Article
Language:	English
Published:	Switzerland John Wiley & Sons, Inc 01-05-2020 John Wiley and Sons Inc
Subjects:	Adults Animals Apoptosis Brain Brain - pathology Caspase CD163 antigen CD206 Cell death Cell proliferation Encephalitis Female HIV Human immunodeficiency virus Immunofluorescence Immunohistochemistry Infants Infections Kinases Macaca mulatta macrophage Macrophages Macrophages - pathology Male Microglia Necroptosis Necroptosis - physiology Neonates perivascular macrophage Populations Primates Protein kinase Simian Acquired Immunodeficiency Syndrome - pathology Simian Immunodeficiency Virus Viruses CD206 apoptosis macrophage perivascular macrophage HIV necroptosis
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Summary:	We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV‐infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus‐induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV‐infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV‐infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIV‐infected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single‐positive population in addition to the double‐positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163− PVMs in SIV‐infected infants were positive for cleaved caspase‐3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptor‐interacting protein kinase‐3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM‐dependent SIVE and the limited size of the virus reservoir in the infant brain.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to the work.
ISSN:	1015-6305 1750-3639
DOI:	10.1111/bpa.12808