HCWang 2 2013

Vaccinia A27 Protein Structure Revealed to Regulate Virus Cell Membrane Fusion with Host

Research teams led by Dr. Andrew H.-J. Wang (IBC) and Dr. Wen Chang (IMB) have joined the effort to solve the crystal structure of a vaccinia envelope A27 protein and showed that the protein trimer is the structural unit critical for vaccinia virus egress as well as controlling viral fusion suppressor complex formation. The findings shed light on the viral fusion regulation mechanism of vaccinia virus, a member of poxvirus family that also contains variola virus, the etiological disease of smallpox disease. Revelation of viral membrane protein structure will aid in design of improved vaccine in the future. The research was published in PLoS Pathogens on August 23, 2013.

Poxvirus family contains many pathogenic members such as mousepox, sheepox, and monkeypox viruses. Vaccinia virus is considered safe to be used for induction of protective immune responses in humans. Researches now are focused on understanding vaccinia virus structure proteins in order to improve the future vaccine design. A27 mediates the attachment of mature vaccinia virus to cell surface heparan sulphate during entry to its host and mediates mature virus transport in infected cells. A27 also tethers the viral fusion suppressor protein A26 to mature virions.

The two teams generated a series of mutant vaccinia viruses that interrupt A27 protein-protein contact interface resulting in attenuation of virus egress and virus spreading in cells basing on the protein’s crystal. They have also demonstrated that A27 protein complex formation through the coiled-coiled domain is crucial to its biological activity in vivo, and revealed how A27 regulates virus-induced membrane fusion through its ability to form complexes with A26 protein. Given that A27 is a critical target in neutralizing antibodies against pathogenic poxvirus infection in humans, their findings provide a structural basis for the development of anti-pox drugs and vaccines.

Full article available at: http://dx.plos.org/10.1371/journal.ppat.1003563

Authors : Tao-Hsin Chang, Shu-Jung Chang, Fu-Lien Hsieh, Tzu-Ping Ko, Cheng-Tse Lin, Meng-Ru Ho, Iren Wang, Shang-Te Danny Hsu, Rey-Ting Guo, Wen Chang, and Andrew H.-J. Wang

Updated : 2013.09.05

A27 ReHigh 2013