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- Title
Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.
- Authors
Anjie Zhen; Rezek, Valerie; Youn, Cindy; Lam, Brianna; Chang, Nelson; Rick, Jonathan; Carrillo, Mayra; Martin, Heather; Kasparian, Saro; Syed, Philip; Rice, Nicholas; Brooks, David C.; Kitchen, Scott C.; Zhen, Anjie; Brooks, David G; Kitchen, Scott G
- 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.
- Subjects
TYPE I interferons; THERAPEUTICS; HIV infections; IMMUNOSUPPRESSION; T cells; CELLULAR signal transduction; ANIMALS; BIOLOGICAL models; CHRONIC diseases; HIV; INTERFERONS; MICE; ANTIRETROVIRAL agents; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 1, p260
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI89488