Title | Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Zhen A, Rezek V, Youn C, Lam B, Chang N, Rick J, Carrillo M, Martin H, Kasparian S, Syed P, Rice N, Brooks DG, Kitchen SG |
Journal | J Clin Invest |
Volume | 127 |
Issue | 1 |
Pagination | 260-268 |
Date Published | 2017 Jan 03 |
ISSN | 1558-8238 |
Keywords | Animals, Anti-Retroviral Agents, CD8-Positive T-Lymphocytes, Chronic Disease, Disease Models, Animal, HIV Infections, HIV-1, Humans, Interferon Type I, Mice, Mice, Knockout |
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. |
DOI | 10.1172/JCI89488 |
Alternate Journal | J. Clin. Invest. |
PubMed ID | 27941243 |
PubMed Central ID | PMC5199686 |
Grant List | R01 AI085043 / AI / NIAID NIH HHS / United States P30 AI028697 / AI / NIAID NIH HHS / United States R21 AI110306 / AI / NIAID NIH HHS / United States R01 AI078806 / AI / NIAID NIH HHS / United States T32 AI060567 / AI / NIAID NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm