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Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection

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Abstract

This review outlines the neuropathogenesis of HIV, from initial HIV entry into the central nervous system (CNS) to chronic infection, focusing on key advancements in the last 5 years. Discoveries regarding acute HIV infection reveal timing and mechanisms of early HIV entry and replication in the CNS, early inflammatory responses, and establishment of genetically distinct viral reservoirs in the brain. Recent studies additionally explore how chronic HIV infection is maintained in the CNS, examining how the virus remains in a latent “hidden” state in diverse cells in the brain, and how this leads to sustained pathological inflammatory responses. Despite viral suppression with antiretroviral therapy, HIV can persist and even replicate in the CNS, and associate with ongoing neuropathology including CD8 + T-lymphocyte mediated encephalitis. Crucial investigation to advance our understanding of the immune mechanisms that both control viral infection and lead to pathological consequences in the brain is necessary to develop treatments to optimize long-term neurologic health in people living with HIV.

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Acknowledgements

We express our gratitude to the many individuals who have volunteered to partake in the studies reviewed here. Without their generosity, this work would not be possible.

Funding

LK is supported by NIH training grant 5T32GM136651-02. SS is supported by grants from the NIH including R01MH125737, R01MH125396, R01MH106466, and UM1DA051410.

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  1. Department of Neurology, Yale University School of Medicine, 300 George Street, Room 8300c, New Haven, CT, 06520, USA

    Lauren Killingsworth & Serena Spudich

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Correspondence to Serena Spudich.

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This article is a contribution to the special issue on: Neuroimmune Interactions in Health and Disease - Guest Editors: David Hafler & Lauren Sansing

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Killingsworth, L., Spudich, S. Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection. Semin Immunopathol 44, 709–724 (2022). https://doi.org/10.1007/s00281-022-00953-5

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