Get access

Immune privilege and HIV-1 persistence in the CNS

Authors

  • Yuri Persidsky,

    Corresponding author
    1. Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA.
    2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
    3. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
    Search for more papers by this author
  • Larisa Poluektova

    1. Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE, USA.
    2. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
    Search for more papers by this author

Yuri Persidsky
Departments of Pathology and Microbiology
985215 Nebraska Medical Center
Omaha, NE 68198-5215, USA
Tel.: 402 559-3549
Fax: 402 559-8922
E-mail: ypersids@unmc.edu

Abstract

Summary:  Human immunodeficiency virus-1 (HIV-1) neuroinvasion occurs early (during period of initial viremia), leading to infection of a limited amount of susceptible cells with low CD4 expression. Protective cellular and humoral immunity eliminate and suppress viral replication relatively quickly due to peripheral immune responses and the low level of initial central nervous system (CNS) infection. Upregulation of the brain protective mechanisms against lymphocyte entry and survival (related to immune privilege) helps reduce viral load in the brain. The local immune compartment dictates local viral evolution as well as selection of cytotoxic lymphocytes and immunoglobulin G specificity. Such status can be sustained until peripheral immune anti-viral responses fail. Activation of microglia and astrocytes, due to local or peripheral triggers, increases chemokine production, enhances traffic of infected cells into the CNS, upregulates viral replication in resident brain macrophages, and significantly augments the spread of viral species. The combination of these factors leads to the development of HIV-1 encephalitis-associated neurocognitive decline and patient death. Understanding the immune-privileged state created by virus, the brain microenvironment, and the ability to enhance anti-viral immunity offer new therapeutic strategies for treatment of HIV-1 CNS infection.

Ancillary