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Limited HIV-associated neuropathologies and lack of immune activation in sub-saharan African individuals with late-stage subtype C HIV-1 infection

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Abstract

Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators.

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Data availability

The data that support the findings of this study are available on request from the corresponding author [CW].

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Acknowledgements

We are grateful to the deceased and their families for participation in this study, and to the team members and investigators of University of Zambia/University Teaching Hospital. We also thank our former lab member, Dawn Eggert, for her work and effort on sample collection and processing.

Funding

Fogarty International D43 TW010354; National Cancer Institute U54CA221204, R01NS074903 and R01DA044920 through CW. PJ, and VM are Fogarty Fellows.

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Authors and Affiliations

  1. Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA

    Zhou Liu & Charles Wood

  2. Department of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Zhou Liu, Guobin Kang, John T. West & Charles Wood

  3. Department of Pathology and Microbiology, University of Zambia School of Medicine, Lusaka, Zambia

    Peter Julius

  4. Department of Pathology, University Teaching Hospital, Lusaka, Zambia

    Victor Mudenda

  5. Department of Pathology and Medicine, Louisiana Cancer Research Center, Louisiana State University Health Sciences Center, New Orleans, LA, USA

    Luis Del Valle

  6. 1700 Tulane Avenue, LCRC Rm 614, New Orleans, LA, 70112, USA

    Charles Wood

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  1. Zhou Liu
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Contributions

ZL performed experiments, analyzed the data, and wrote the manuscript. PJ led sample collection. VM aided with tissue collection and processing and obtaining clinical information. GK conducted H&E staining. LDV provided pathology expertise and helped edit the manuscript. JTW supported methodology, data analysis, and manuscript editing. CW conceived of and led the study.

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Correspondence to Charles Wood.

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Liu, Z., Julius, P., Mudenda, V. et al. Limited HIV-associated neuropathologies and lack of immune activation in sub-saharan African individuals with late-stage subtype C HIV-1 infection. J. Neurovirol. (2024). https://doi.org/10.1007/s13365-024-01219-6

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