日時：	2019年10月9日 （水）15：00～16：00
場所：	京都大学 ウイルス再生研　1号館 1階　会議室
演者：	Vanessa Sancho Shimizu博士 (Imperial Collage of London)
演題：	Using genetics to understand herpes encephalitis

講演要旨

HSE is a rare and life-threatening infection caused by Herpes Simplex Virus-1 (HSV-1), causing infection and inflammation in the brain. Innate immune effectors such as type I interferons (IFN) are critical in controlling HSV-1 infection via recognition by toll like receptors (TLRs). Previous studies have identified single gene mutations in the TLR3-IFN pathway in a subset of children with HSE. These patients have impaired antiviral IFN production leading to increased viral susceptibility. Recently, genes in this pathway were found to play a role in the process of autophagy. Autophagy is involved in the recycling of damaged cellular components, and in elimination of pathogens. A growing number of reports suggest its anti-viral role in various infections, including HSV1. Whilst studies have shown the non-redundant role of TLR3-IFN signalling pathway in HSV1 defence, the role of autophagy in HSV1 infection and HSE pathogenesis remains elusive. In this study, we characterize the role of autophagy in the context of HSV1 infection, using human dermal fibroblasts derived from HSE patients harbouring mutations in components of the TLR3-IFN pathway. We describe spatially and temporally distinct autophagy phenotypes following HSV1 infection: cytoplasmic and perinuclear autophagosome formation occurring early and late in infection respectively. The early cytoplasmic autophagosomes were found to be TBK1-dependent but TLR3- and IFN-independent, and can be induced in neighbouring non-infected cells. Furthermore, we demonstrated the cytoprotective nature of autophagy in HSV1 infection. We highlight the importance of IFNs and autophagy in HSV1 infection and summarize the lessons learned from genetic and molecular investigations of HSE patients.

（言語：英語　Language: English）