No. 89

June 2013

Headline News Innovation and Development

Applied Technology

Basic Science

Cooperation between CAS and Local Authorities

Bioscience International Cooperation Brief News Geoscience Hightlight Events
Innovation and Development

Development on CA16 Vaccine Gains New Advancement

Dr. Huang Zhong¡¯s group in the Institut Pasteur of Shanghai (IPS), CAS has made progress on the development of CA16 vaccine. Coxsackievirus A16 (CA16) is one of the main pathogens that cause hand, foot and mouth disease, which frequently occurs in children. Until now there is no vaccine for CA16. This study successfully evaluated the active protective effects of candidate CA16 vaccine, based on the mouse-adapted strain called CA16-MAV developed by Huang¡¯s group. The inactivated whole virus was obtained by culturing CA16 virus in Vero cells, and then inactivated with chemical treatment, followed by ultra centrifugation. In this study, the inactivated whole-virus vaccines derived from two CA16 clinical isolates were able to induce CA16-specic antibody and IFN-secreting T-cell responses in mice. The resulting anti-CA16 mouse sera neutralized both homologous and heterologous CA16 clinical isolates, as well as CA16-MAV, which is capable of infecting 14-day-old mice. Passive transfer of anti-CA16 neutralizing sera partially protected neonatal mice from lethal challenge by a clinical isolate CA16-G08. More signicantly, active immunization of mice with the inactivated vaccines conferred complete protection against lethal infection with CA16-MAV. Collectively, these results provide a solid foundation for further development of inactivated whole-virus CA16 vaccines for human use. The result was published online in Vaccine in March 2013.

Mechanism of CCM3-MST4 Hetreodimer Assembly Revealed

A research team led by Prof. Zhou Zhaocai and Prof. Zhang Lei at the Shanghai Institute of Biochemistry and Cell Biology, CAS published a paper entitled ¡°Structural mechanism of CCM3 heterodimerization with GCK-¢ó Kinases in the magazine Structure on April 2, 2013. The work reveals mechanism of cerebral cavernous malformation 3 and GCK-¢ó hetreodimer assembly. By determining the structures of the MST4 in complex with CCM3 using Se-Met substitute crystal, Zhang Meng, Shi Zhubing, and Jiao Shi from Prof. Zhou¡¯s group revealed that a hydrophobic core on the interface accounts for the complex assembly. Structural-based mutational analysis identified a few important residues on CCM3 and MST4 that are required for CCM3-MST4 interaction. Structure comparison of MST4 C-terminal domain with CCM3 N-terminal domain reveals a striking similarity. GCK-¢ó kinases and CCM3 utilize a shared dimerization module to form homodimer or heterodimer. A linker region accounts for the conformational flexibility of CCM3, leading to drastic change of the relative orientation between the dimerization domain and FAT domain of CCM3. In cellular assay, structure guided mutational studies indicate that MST4 and CCM3 complex promotes cell proliferation and cell migration in Hale cells and Ovcar-3 cell, respectively. CCM3 forms heterodimer with distinct members of GCK-¢ó kinases in a similar manner, but induces differential cellular effects most likely due to distinct substrate specificity of different members of GCK-¢ó subfamily. Collectively this work provides a structural framework and functional insights into the cross-talk between GCK-¢ó and CCM3.

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