Cognitive consequences of a sustained monocyte type 1 IFN response in HIV-1 infection.

TitleCognitive consequences of a sustained monocyte type 1 IFN response in HIV-1 infection.
Publication TypeJournal Article
Year of Publication2014
AuthorsPulliam, L
JournalCurr HIV Res
Date Published2014
KeywordsAnimals, Antiviral Agents, Cognition, External, HIV Infections, Humans, Interferon-alpha, Monocytes

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.

Alternate JournalCurr HIV Res
PubMed ID24862334
PubMed Central IDPMC4175740
Grant ListR01 MH096673 / MH / NIMH NIH HHS / United States
R21 MH112483 / MH / NIMH NIH HHS / United States