IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection

Kerur, N. et al. Cell Host Microbe (2011) 9:363-375

Speaker: Ya-Ling Lee (李雅玲)                                     Time: 13:10~14:00, Nov.16, 2011

Commentator: Dr. Chia-Ling Chen (陳嘉玲博士)       Place: Room 601

Abstract

        Inflammasomes are multiprotein complex that consist of three proteins including a sensor protein, an adaptor protein known as the apoptosis-associated speck-like protein containing a CARD (ASC) , and procaspase-1¹. Inflammasomes activated by pathogens exist in the cytoplasm andinduce caspase-1 activation and interleukin-1β maturation. However, the presence and function of inflammasomes in the nucleus remain unclear. In the present study, the authors used kaposi sarcoma-associated herpesvirus (KSHV) which replicates in the nucleus to address this issue. They found that after 2 hours post-infection, KSHV induced caspase-1 activation and interleukin-1β maturation. At that time, the majority of activated caspase-1 was co-localized with ASC in the nucleus and translocated into the perinuclear area after 8 hours post-infection. They further found that interferon gamma-inducible protein 16 (IFI16) was the sensor protein interacted with ASC in the nucleus of KSHV-infected cells. The IFI16-ASC interaction was absent in the cells infected with vaccinia virus, a virus replicates in the cytoplasm. Knocking down IFI-16 expression in KSHV-infected cells abolished the activation of caspase-1 and interleukin-1β maturation. Reconstitution of IFI16 inflammasome in HEK-293T cells induced interleukin-1β maturation after KSHV infection. Taken together, these results show that IFI16 acts as a nuclear pathogen sensor and the inflammasome functions in not only the cytoplasm but also the nucleus.

Reference

1.     Gross, O. et al. The inflammasome: an integrated view. Immunol Rev (2011) 243: 136-151.