4.5 Review

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

Journal

SEMINARS IN IMMUNOPATHOLOGY
Volume 44, Issue 5, Pages 709-724

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00281-022-00953-5

Keywords

HIV; Central nervous system; Cerebrospinal fluid; Neurovirology; Neurological infections; CSF HIV escape; HIV reservoir

Funding

  1. NIH training grant [5T32GM136651-02]
  2. NIH [R01MH125737, R01MH125396, R01MH106466, UM1DA051410]

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This review summarizes the neuroplathogenesis of HIV, covering the virus's entry, replication, and persistence in the central nervous system (CNS). Recent advancements have shed light on the timing and mechanisms of early HIV infection in the CNS, establishment of distinct viral reservoirs, and maintenance of chronic infection. Despite antiretroviral therapy, HIV can persist and replicate in the CNS, causing ongoing neuropathology. Understanding the immune mechanisms in controlling viral infection and their effects on the brain is crucial for optimizing long-term neurologic health in individuals with HIV.
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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