Start main content



May 17, 2019

RPG Seminar Series (Speaker: Mr. LUI Wai Yin / Miss ZOU Wenjun)

Date: Friday, 17 May 2019

Venue: Seminar Room 4, G/F
Laboratory Block, Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Time: 5:00 p.m.

Title: Suppression of cGAS-STING-mediated innate immune responses by Epstein Barr Virus-encoded large tegument protein BPLF1 through deubiquitination
Speaker: Mr. LUI Wai Yin (MPhil candidate)

Epstein-Barr virus (EBV) is an oncogenic virus linked with 2% human malignancies such as nasopharyngeal carcinoma. The prevalence of EBV infection suggests it may have developed effective innate evasion strategies. In this project we performed a functional screen to identify EBV deubiquitinase (DUB) BPLF1 as a potent antagonist of type I interferon production induced by DNA sensors cGAS and STING. The large tegument BPLF1 exhibited prominent suppression on cGAS-STING-, and TBK1-induced interferon production. This effect disappeared when Cys61 of BPLF1 was substituted with Ala, which rendered its DUB domain catalytically inactive. This indicated DUB activity is required for BPLF1's innate immunosuppressive property. BPLF1 was an active DUB for K63-, K48- and K27- linked ubiquitin chains on STING and for K63- and K48- linked ubiquitin chains on TBK1. Our findings suggest that EBV-encoded tegument BPLF1 mitigates innate immune responses through its DUB activity on STING and TBK1 of innate immune signaling.

Title: Transcriptional regulation of TAX1BP2, a putative tumor suppressor in hepatocellular carcinoma
Speaker: Miss ZOU Wenjun (MPhil candidate)

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancer in South East Asia, mainly due to the high prevalence rate of chronic hepatitis B virus (HBV) infection. The prognosis of HCC patient is often undesirable due to late diagnosis and highly metastatic nature of HCC. Together with a limited choice of chemotherapy, this makes HCC a critical health threat in Hong Kong. Thus, better treatment modality is desperately required for HCC. TAX1 binding protein 2 (TAX1BP2), which is first identified as a novel binding partner of TAX1, an oncoprotein encoded in HTLV I virus, is frequently underexpressed in HCC. Underexpression of TAX1BP2 is associated with poorer survival outcome of patient. To understand how TAX1BP2 is downregulated in HCC, we examined the transcriptional regulation of TAX1BP2. By LASAGNA software, I predicted the potential transcriptional factors binding sites on TAX1BP2 promoter and showed that deletion of the binding sites for HNF-4α transcription factor resulted in a significant decrease in TAX1BP2 promoter activity. Consistently, ectopic expression of HNF4α upregulated the promoter activity, mRNA and protein expression levels of TAX1BP2. Interestingly, ectopic expression of HBx, an oncoprotein encoded by HBV, was able to inhibit HNF-4a and suppress TAX1BP2 protein expression. Furthermore, the HBx mediated suppression of TAX1BP2 promoter activity could be rescued by ectopic expression of HNF-4a, indicating that HBx and HNF-4a works within the same signaling pathway. Taken together, these results suggested that HNF-4 is an activating transcription factor of TAX1BP2. The elucidation of a HBx-HNF4α-TAX1BP2 pathway provides novel insight into the molecular mechanism underlining chronic HBV infection associated hepatocarcinogenesis.