title: Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.
abstract: Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection.
authors.forename: Anjie
authors.initials: A
authors.lastname: Zhen
authors.forename: Valerie
authors.initials: V
authors.lastname: Rezek
authors.forename: Cindy
authors.initials: C
authors.lastname: Youn
authors.forename: Brianna
authors.initials: B
authors.lastname: Lam
authors.forename: Nelson
authors.initials: N
authors.lastname: Chang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rick
authors.forename: Mayra
authors.initials: M
authors.lastname: Carrillo
authors.forename: Heather
authors.initials: H
authors.lastname: Martin
authors.forename: Saro
authors.initials: S
authors.lastname: Kasparian
authors.forename: Philip
authors.initials: P
authors.lastname: Syed
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rice
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
authors.forename: Scott G
authors.initials: SG
authors.lastname: Kitchen
mesh_terms: D000818:Animals; D044966:Anti-Retroviral Agents / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D044966:Anti-Retroviral Agents; D007370:Interferon Type I