Scientists identify a mutation that influences infectivity of flaviviruses
Flavivirus is a genus of viruses in the family Flaviviridae, including about 75 species. It includes the West Nile virus, dengue fever virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and some other viruses, which constitute a significant threat to global health. Flaviviruses are typically spread to humans by infected ticks or mosquitoes. Until now, there is no effective treatments or vaccines for many of the viruses. So a lot of scientists have been making efforts to find ways to combat flaviviruses. Among them, a team led by Theodore Pierson from National Institutes of Health focuses on the interactions between flaviviruses and antibodies produced by the body's immune system.
Pierson's team investigated the effects of mutations in the envelop (E) protein of flaviviruses. The E protein is a structurally flexible protein: it can change its shape in a process called "viral breathing," which alternately hides and exposes certain parts of the protein. Although E protein has been implicated in infection, its action is not fully understood.
Using the West Nile virus E protein, the researchers identified a single mutation called T198F at a region of the protein that regulates viral breathing. The mutation resulted in a great increase in sensitivity of E protein to neutralization by antibodies. In the following experiments, they found that introduction of the T198F mutation into dengue virus made a hidden protein region more vulnerable to antibodies, and decreased virus stability in solution. Mice experiments showed that West Nile virus carrying the mutation had reduced infectivity.
The study, which is published in PLoS Pathogens, provides insight into the molecular basis of flavivirus breathing, although there are still many unanswered questions.
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