Unknown

Dataset Information

0

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.

SUBMITTER: Zhen A 

PROVIDER: S-EPMC5199686 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Targeting type I interferon-mediated activation restores immune function in chronic HIV infection.

Zhen Anjie A   Rezek Valerie V   Youn Cindy C   Lam Brianna B   Chang Nelson N   Rick Jonathan J   Carrillo Mayra M   Martin Heather H   Kasparian Saro S   Syed Philip P   Rice Nicholas N   Brooks David G DG   Kitchen Scott G SG  

The Journal of clinical investigation 20161212 1


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  ...[more]

Similar Datasets

| S-EPMC4232062 | biostudies-other
| S-EPMC4745252 | biostudies-literature
| S-EPMC5138643 | biostudies-literature
| S-EPMC3309969 | biostudies-literature
2008-02-19 | GSE9927 | GEO
2021-10-11 | GSE163365 | GEO
| S-EPMC3196770 | biostudies-literature
| S-EPMC6561747 | biostudies-literature
| S-EPMC5578711 | biostudies-literature
| S-EPMC4263756 | biostudies-literature