Duke-NUS finds cause for vaccine-resistant dengue virus

September 30, 2019

The dengue virus (DENV) can cause its victims to suffer either mild dengue fever or fatal dengue haemorrhagic fever and dengue shock syndrome. Dengue infections are particularly prevalent in tropical and sub-tropical regions.  Recently, a research team from Singapore’s Duke-NUS Medical School (Duke-NUS) found that the virus changes its shape through mutations, at varying temperatures, to evade vaccines and therapeutics against it.

Virulent strain DENV2 is known to exist as smooth spherical surface particle at 29 degrees Celsius, but will rapidly change to a bumpy-surfaced particle at human physiological temperature, or at 37 degrees Celsius, thus enabling the virus to evade the immune system of the human host.

Of this ability, Xin-Ni Lim, from Duke-NUS’ Emerging Infectious Diseases (EID) Programme, said mutations in the virus’ specific protein structure can help it evade the system and causes vaccines and therapeutics to be ineffective against the virus.

When compared to laboratory-adapted viruses, the majority of DENV2 strains obtained from patients maintained smooth surface structure at 37 degrees Celsius. These clinical strains, however, took on a bumpy surface structure at 40 degrees Celsius, the temperature of a fever. By cross-referencing different stages of infection, this could give rise to new vaccine developments/treatments for dengue disease.

Dr. Sheemei Lok of Duke-NUS’ EID Programme, explains, “For prevention of disease through vaccines that are administered to the patient before dengue infection, we should use those that are effective against the smooth surface virus; when it comes to patients displaying fever symptoms, treatment strategies effective against the bumpy surface particles should be implemented.”

Computational modelling approaches were used in the study to predict why particles from different DENV2 strains are more, or less, adept at morphing from the smooth- to bumpy-surfaced structures. While the lab-adapted DENV2 may not be a good model for research, as its structure is different from the clinical strains isolated from patients, the researchers are planning to study other DENV serotypes to find out if there are other significant structural differences that may help in therapeutics and vaccine development.


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