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Current HIV Research
ISSN (Print): 1570-162X
ISSN (Online): 1873-4251
DOI: 10.2174/1570162X12666140526113544

Cognitive Consequences of a Sustained Monocyte Type 1 IFN Response in HIV-1 Infection

Author(s): Lynn Pulliam
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 cognitive function.
Graphical Abstract:
Cognition, HIV-1, HCV, impairment, interferon, monocyte.
Veterans Affairs Medical Center (113A), 4150 Clement St., San Francisco, CA 94121, USA.