Poxvirus Entry Mechanism and Membrane Fusion Regulation
I. Investigation of vaccinia virus membrane fusion complex
Vaccinia virus is a large enveloped DNA virus and belongs to the poxvirus family. Vaccinia virus has a wide host
range and infects different cell types in vitro and in vivo. Vaccinia mature virus contains four enveloped proteins for
cell attachment and a fusion complex of eleven enveloped proteins for membrane fusion. We previously identified
four mature virus attachment proteins and studied the viral endocytic pathway. We are now focusing on vaccinia
virus fusion protein complex. We aim to dissect the structure and function of each components of viral fusion
complex in order to understand the membrane fusion mechanism. In the future, we will expand our study into other
DNA viruses such as African swine fever virus.
II. Investigation of vaccinia viral fusion suppressor proteins
Because virus-mediated membrane fusion often occurs in acidic endosomes and acidic pH serves as an
environmental cue to induce conformational changes of viral fusion protein to execute membrane fusion. We
recently identified a unique protein A26 on mature virus which, upon acidification, had conformational changes
through protonation of specific His residues, providing a critical mechanism to de-repress fusion complex leading
to membrane fusion activation. Therefore, vaccinia virus not only has a complicated fusion protein complex but also
has a unique viral fusion suppressor protein, such as A26, to control where and when membrane fusion should be
activated during virus entry. In the future, structure and functional analyses of viral fusion suppressor proteins will
be explored.
III. Host specific influences on virus entry, replication and egress
When we deleted A26 ORF from wild type vaccinia virus WR strain (WT-WR), we found that WRΔA26 infections into
murine bone marrow derived macrophages (BMDM) were better than WT-WR virus with high levels of early and late
gene expression. Subsequently analyses revealed that WT-WR entry into BMDM induced type 1 interferon response
whereas WRΔA26 was able to escape such innate immune detection. Currently, we are trying to understand the
cellular factors involved in such a differential interferon induction pathway. We anticipate such knowledge will expand
the usefulness of designing vaccinia virus as a better vaccine vector or an oncolytic agent for cancer treatment.
- PDF, 1989-1992, Center for Cancer Research, MIT, USA
- PDF, 1988, Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, USA
- Ph.D., 1988, Department of Microbiol. & Immunol., University of Washington at Seattle, USA
- BS, 1982, Department of Agriculture Chemistry, National. Taiwan University
- 2002, Academia Sinica Early-Career Investigator Research Achievement Award
- 2006, Research Excellence Award, National Science and Technology Council
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