Dengue virus replication halted by regulatory protein

5 July 2018

Dengue virus is the most prevalent mosquito-borne viral pathogen, causing an estimated 100 million infections worldwide every year according to the World Health Organisation.

A recent research published by Dr Sumana Sanyal (Croucher Non-Clinical Assistant Professorship 2017) of the University of Hong Kong could possibly provide new insights into the development of antivirals and vaccine against dengue.

Ubiquitin is a small regulatory protein that can be added on or removed from other proteins via a mechanism called ubiquitin modification.

Sanyal and her colleagues found that unmodified AUP1, a lipid droplet membrane protein is necessary for dengue virus reproduction. Aup1 associates with dengue viral protein and relocalise from lipid droplets to lipid degradative vesicles.

Ubiquitin modification disrupted the interaction between Aup1 and dengue virus and inhibited the enzymatic activity of Aup1, defective lipid droplet degradation and inhibited virus production.

Interfering ubiquitin modification appears to be a general phenomenon employed during the biogenesis of viruses from the same family as dengue, including Zika and West Nile virus.

The findings were published in Cell Host & Microbe.

Professor Hidde Ploegh, Senior Investigator at the Boston Children's Hospital added, “Sumana's work is satisfying for multiple reasons: understanding in detail of how viruses go about their business is a prerequisite for devising a workable strategy to fight these nasty pathogens. Doubly satisfying because this study, in unexpected fashion, connects the work of a former graduate student, Elizabeth Klemm, on the AUP1 protein with Sumana, a former postdoc while at the Whitehead Institute. It's nice to keep it in the family, sort of. A terrific piece of work. ”

Dr Sumana Sanyal is a biochemist by training with an interest in aspects of host pathogen interactions including influenza, dengue and related viruses. She obtained her PhD from Cornell University, USA and postdoctoral training from the Whitehead Institute/MIT. Her current research includes identification and characterization of host factors important in virus pathogenesis. Using a combination of genetics and proteomics-based approaches her research group is investigating how post translational modifications, especially the ubiquitylation machinery, are targeted and alter protein function during cellular perturbations such as in virus infections, either to facilitate replication and pathogenesis or in installing a host immune response.

To view Dr Sanyal's Croucher profile, please click here