Dengue virus seen under an electron microscope. Image credit: Sanofi Pasteur, Institut Pasteur (CC BY-NC-ND 2.0)
Viruses are constantly evolving as a result of mutations in their genetic material and environmental pressures. Viruses switching between insects and mammals face unique evolutionary pressures because they must retain their ability to infect both types of organisms. Yet, the mutations in a virus that may be beneficial in an insect may be different from the ones that may be beneficial in a mammal. Mutations in one host may be even harmful in the other.
To learn more about how such viruses thrive as they switch between hosts, Dolan, Taguwa et al. studied the dengue virus, which causes over 390 million infections and over 10,000 deaths each year around the globe. They compared the mutations that occurred as the virus multiplied in human and mosquito cells grown in a laboratory.
In the experiments, they used a method called ultra-deep RNA sequencing to identify every change that occurred in the genetic material of the virus each time it multiplied. They determined whether the mutations were beneficial or harmful based on whether they became more common – suggesting they helped the virus survive – or whether they did not persist because they were likely harmful or even fatal to the virus.
The experiments showed that many harmful mutations constantly occur in the virus, in both human and mosquito cells. Beneficial changes happen rarely, and those that do are usually only helpful in one type of cell. Fatal mutations tended to occur in parts of the genetic material that encodes regions in the viral proteins that must remain the same. These structural elements appear to be essential to the virus’s survival and unable to undergo change, which makes them good targets for antiviral drugs or vaccines. The techniques used in the study may be useful for investigating other viruses and for understanding the evolutionary constraints on viruses more generally. This may help scientists develop antiviral drugs or vaccines that will remain effective even as viruses continue to evolve and mutate.
