RNA viruses are characterized by a high mutation rate; although some mutations are neutral or adaptive, many RNA viral progeny are defective and purged by selection. Hence, only a fraction of the virus genomes found in an individual host may be viable enough to transmit to new hosts. Eddie Holmes and collaborators have investigated how the genetic diversity of dengue (DENV-1) viruses changes through time, using samples isolated from individual humans and mosquitoes in Myanmar.
The researchers found high within-host prevalence of apparently defective viral genetic sequences. An especially widespread mutation involved the insertion of a stop codon in an essential envelope gene partway along the genome. Intriguingly, an evolutionary lineage of "defective" viruses containing this stop codon was successfully transmitted for at least 18 months in humans and mosquitoes — even though the mutation appears to make the viral surface envelope protein non-viable, and may also halt translation of downstream proteins.
In a 2006 Science paper describing their findings, the researchers propose that coinfection with functional viruses allowed the defective genomes to persist in the population: the mutant genomes may have been able to transmit from host to host by "parasitizing" functional proteins from other dengue viruses coinfecting the same cells, a process known as complementation.
This work has three important implications:
- It illustrates that consensus genetic sequences (commonly used to construct phylogenetic trees) can give a misleading impression of genetic diversity in the viral population
- It suggests that it is not uncommon for a single cell to be multiply infected by different variants of a virus
- It shows that complementation, whilst well documented in vitro, may also be an important evolutionary force in vivo.
Written By: John Aaskov, Katie Buzacott, Hlaing Myat Thu, Kym Lowry, & Edward C. Holmes
Paper Url: http://www.sciencemag.org/cgi/content/abstract/311/5758/236
Journal: 311: 236-238
Journal Reference: 311: 236-238
Paper Id: 10.1126/science.1115030