Hisashi Akiyama, Ph.D.
Department of Microbiology, Boston University School of Medicine, Boston, USA
Titel: Innate Immune Activation in HIV Infection
Zeit: 17:00 Uhr s.t.,
Ort: TWINCORE Seminar room 0.02
Ansprechpartnerin: <link mail internal link in current>Jun.-Prof. Christine Goffinet
Abstract:
Systemic chronic immune activation and T cell dysfunction are hallmarks of HIV-1 infection. Despite long-term viral suppression by combination antiretroviral therapy (cART), immune activation and inflammation persist in the majority of HIV-infected individuals on cART, and is associated with excess risk of mortality and morbidity. Low-levels of type I interferon (IFN-I) are thought to be a driving force for immune activation and T cell exhaustion in HIV-1 infected individuals on cART. Many factors have been attributed to cause this aberrant immune activation in vivo, such as bacterial endotoxin or co-infections. However, the causative mechanisms for persistent IFN-I signaling have remained unclear. Since tissue-resident myeloid cells can remain persistently infected with HIV-1 even in individuals on cART, we hypothesized that persistent infection of myeloid cells may contribute to immune activation and T cell dysfunction.
Here we demonstrate that that expression and Rev–CRM1-dependent nuclear export of intron-containing HIV-1 RNA activates host sensing mechanisms and IFN-I-dependent pro-inflammatory responses via MAVS in productively infected macrophages. Furthermore, HIV-1 infection-induced activation of macrophages, in turn, leads to exhaustion of co-cultured autologous T cells. This study suggests that use of HIV RNA expression inhibitors as adjunct therapy might abrogate aberrant inflammation and restore immune function in HIV-infected individuals on cART.