Dengue virus becomes resistant to vaccines and treatments due to specific protein mutations

Researchers from the Duke-NUS (Duke-NUS) School of Medicine, in collaboration with the Institute of Bioinformatics (BII) of the Agency for Science, Technology and Research (A * STAR), and the medical branch of the University of Texas (UTMB), in the United States, have discovered that the dengue virus changes form as a result of mutations of the protein Envelope (E) in order to avoid vaccines and treatments. The study also gives insight into the types of treatment strategies to use at different stages of the infection. This could lead to new approaches to vaccine development and dengue treatment.

Dengue virus (DENV) infects about 400 million people each year worldwide, with high prevalence in the tropics and subtropics. The virus causes diseases ranging from mild dengue fever to severe dengue fever and dengue shock syndrome.

DENV2 is in the form of smooth spherical surface particles, growing at the physiological temperature of the mosquito (29 ° C). It then changes to bumpy particles at human physiological temperature (37 degrees Celsius). This ability to transform helps the virus to escape the immune system of the human host. Therefore, it is important to understand the mechanism underlying this development for the development of treatments and vaccines.

"Together with Professor Pei-Yong Shi of UTMB, we have discovered that in the laboratory, developed DENV2 strains, mutations of the E protein of the virus cause its transformation into bumpy particles." Structures can render vaccines and therapeutic products ineffective against the virus, "said Ms. Xin-Ni Lim, the lead author of the study that is part of Duke-NUS 'emerging infectious disease program. .

The team also tested four DENV2 strains obtained from patients. They found that, unlike laboratory-adapted viruses, the majority of these clinical strains maintained a smooth surface structure at 37 degrees Celsius. However, at 40 degrees Celsius fever temperature, all strains of the virus took on a bumpy surface.

"Our study gives a new direction to vaccine development and dengue treatment.For the prevention of diseases through vaccines administered to the patient prior to dengue infection, we should use those that are effective against dengue fever. Smooth Surface Virus: When it comes to patients with fever symptoms, effective treatment strategies against bumpy surface particles need to be implemented, "said Dr. Sheemei Lok, Professor at Duke-NUS & # 39; EID and the corresponding author of this study.

"This study is a first step towards a better understanding of how DENV2 responds and adapts to the host's immune defenses, and we have been able to use computational modeling methods to predict why particles of different DENV2 strains are more or less able to transform By better understanding the interactions between the virus and the host, we can develop better treatments and vaccines to treat or prevent infections and thus contribute to public health outcomes. " said Dr. Peter Bond, principal investigator of A * STAR's BII.

The results of the study also show that the laboratory-adapted DENV2 may not be a good model for research because its structure is different from that of clinical strains isolated in patients. The team plans to study other DENV serotypes to determine if there are other possible structural changes.