Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection

Area of Science:

• Neuroscience
• Immunology
• Virology

Background:

• Central nervous system (CNS) abnormalities are detectable during chronic human immunodeficiency virus (HIV) infection.
• The molecular basis for motor and cognitive disorders in the chronic stage of HIV infection remains unclear, despite links between end-stage dementia and brain macrophages/microglia.

Purpose of the Study:

• To investigate the molecular mechanisms underlying CNS dysfunction during the chronic, stable stage of simian immunodeficiency virus (SIV) infection in rhesus monkeys.

Main Methods:

• Utilized SIV-infected rhesus monkeys as a model for HIV infection.
• Assessed CNS functional abnormalities in the chronic infection stage (approx. 2 years post-infection).
• Conducted molecular analysis to identify changes in gene expression within the CNS.

Main Results:

• All infected animals exhibited verified CNS functional abnormalities.
• Both SIV and infiltrating CD8+ T-cells were detected in the CNS.
• Significant upregulation of immune response genes, including CCL5, was observed throughout infection, with CCL5 present in infiltrating lymphocytes during the chronic phase.

Conclusions:

• An altered CNS state exists during the chronic stage of viral infection, characterized by increased immune gene expression.
• This altered state may initially serve to protect against the virus but can lead to long-term damaging processes.
• CCL5 upregulation in infiltrating lymphocytes is a key molecular finding in chronic SIV infection-associated CNS dysfunction.