12 Mar 2015

The Great Escape: Ming Yuan Li and co-workers find that dengue virus uses cellular receptors to move outside of the cell.

The paper, “KDEL Receptors Assist Dengue Virus Exit from theEndoplasmic Reticulum”, published in the journal Cell Reports and the feature was on the cover of the current issue.

Dengue, a mosquito-borne viral disease, is a major health concern in Asia and South America. Clinical manifestations range from flu-like symptoms to a more severe dengue hemorrhagic fever (DHF), and there are currently no vaccines or specific medications for the treatment of the infection. Up to 50-100 million infections are now estimated to occur annually in over 100 endemic countries, putting almost half of the world’s population at risk.

Although dengue cases in Hong Kong are mainly imported and local transmission is extremely rare, HKU-Pasteur Research Pole has been working on this pathogen for many years, after developing a robust cell biological system to study intracellular trafficking of dengue virus.

The life cycle of dengue virus is a complex process relying on specific interactions with host factors that in turn, represent potential targets for functionally interfering with viral replication and pathogenesis. It is unknown whether trafficking and secretion of progeny virus require host intracellular receptors.

Ming Yuan, who carried out this research during her PhD thesis and is now a Research Assistant at HKU-Pasteur Research Pole,asked a crucial question: how does a virus that is assembled inside the cell finds its way out of it?

Her study demonstrates that host KDEL receptors serve as internal receptors that interact with dengue virus structural protein for trafficking from Endoplasmic Reticulum to Golgi of newly formed DENV progeny virions.  These results were obtained in collaboration with teams at Institut Pasteur (Paris) and Institut Pasteur du Laos, with support from BNP-Paribas Corporate and Investment Banking.

This study provides new insight into the molecular mechanisms responsible for dengue progression and pathogenesis during last stage of dengue virus life cycle.

The publication is available here and has been featured in a Research Highlight by Nature Structural and Molecular Biology.