[HTML][HTML] Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs

L Cheng, J Ma, J Li, D Li, G Li, F Li… - The Journal of …, 2017 - Am Soc Clin Investig
L Cheng, J Ma, J Li, D Li, G Li, F Li, Q Zhang, H Yu, F Yasui, C Ye, LC Tsao, Z Hu, L Su…
The Journal of clinical investigation, 2017Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation