Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential

Abstract

The high replication and mutation rates of RNA viruses can result in the emergence of new epidemic variants. Thus, the ability to follow host-specific evolutionary trajectories of viruses is essential to predict and prevent epidemics. By studying the spatial and temporal evolution of chikungunya virus during natural transmission between mosquitoes and mammals, we have identified viral evolutionary intermediates prior to emergence. Analysis of virus populations at anatomical barriers revealed that the mosquito midgut and salivary gland pose population bottlenecks. By focusing on virus subpopulations in the saliva of multiple mosquito strains, we recapitulated the emergence of a recent epidemic strain of chikungunya and identified E1 glycoprotein mutations with potential to emerge in the future. These mutations confer fitness advantages in mosquito and mammalian hosts by altering virion stability and fusogenic activity. Thus, virus evolutionary trajectories can be predicted and studied in the short term before new variants displace currently circulating strains.

Genetic Drift during Systemic Arbovirus Infection of Mosquito Vectors Leads to Decreased Relative Fitness during Host Switching

“…However our calculations of WNV nucleotide diversity during replication in Ae. aegypti were about 4× lower than what was reported during CHIKV infection (Stapleford et al, 2014). These results suggest that the evolutionary outcomes of RNA virus transmission by an arthropod are the product of specific virus-vector interactions that influence genetic drift and selection.…”

“…De novo haplotypes increased in frequency and persisted in multiple tissues but did not cause an accumulation of iLVs compared to the other species; therefore it is not likely that these mutations caused changes in replication fidelity. Multi-step pathways that cause accumulations of viral mutations have been discovered in other arbovirus systems (Stapleford et al, 2014; Tsetsarkin et al, 2014). The principle of a multi-step pathway is that even weak selection for a beneficial mutation allows a network of secondary adaptive mutations.…”

“…CHIKV is capable of adapting to transmission by Aedes albopictus during a single round of infection (Stapleford et al, 2014). WNV evolutionary dynamics have been shown to vary in response to environmental conditions (Bertolotti et al, 2008).…”

“…These include Aedes mosquitoes that may act as a “bridge” between enzootic cycles and mammals, including humans (Kilpatrick et al, 2005). Although it seems clear that infection of mosquitoes leads to genetically complex virus populations (Jerzak et al, 2008; Sim et al, 2015; Stapleford et al, 2014), the impact of any particular mosquito species on WNV population biology has not been determined. In addition, the full range of selective forces acting on WNV during systemic infection of mosquitoes is poorly understood, and important inconsistencies persist in the literature.…”

Chikungunya virus outbreak expansion and microevolutionary events affecting epidemiology and epidemic potential

“…Laboratory studies examining the virus populations generated by mosquito anatomical barriers have also identified mutations that could arise because they confer fitness advantages to their host systems. 81 These reports strongly support early monitoring of viruses emerging in new regions to provide timely information on viral variants that may affect transmission and epidemiology. While modification of the ECSA genotype affected mosquito transmission of the virus in the Eastern hemisphere, no similar or other mutations have been identified in the Asian genotype lineage circulating in the Americas to date.…”