Cognitive Consequences of a Sustained Monocyte Type 1 IFN Response in HIV-1 Infection
Pages 77-84 (8)
With successful antiretroviral therapy, HIV-1-infected subjects can achieve undetectable peripheral viral loads
and immune homeostasis. However, in a subset of individuals on therapy, peripheral monocytes have a gene expression
profile characteristic of a type 1 interferon α (IFN) response. This type 1 IFN response correlates with a number of
pathogenic conditions including neural cell injury and in combination with HCV infection, cognitive impairment. Lessons
from the non-human primate models of pathogenic and nonpathogenic SIV suggest that returning the initial IFN spike in
acute SIV infection to normal allows the immune system to control infection and return to homeostasis. An IFN “alarm”
signature, defined as monocyte activation with overexpression of the type1 IFN genes IFI27 and CD169, would be useful
for identifying a subset of subjects with HIV-1 infection that could progress to a number of pathologies associated with
immune activation including cognitive dysfunction. This strategy is being actively pursued for autoimmune diseases that
are characterized by an IFN signature. Therapies to block the IFN signature are under investigation as a means to reset the
immune system and in a subset of HIV-1-infected subjects may be an adjuvant to standard antiviral therapy to return
Cognition, HIV-1, HCV, impairment, interferon, monocyte.
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