Mosquito- and tick-borne viruses, such as Zika, West Nile, and Powassan, continue to emerge into new areas, and sometimes, they surprise us by causing large outbreaks and severe disease. We use genomics to investigate how they spread (genomic epidemiology), cause disease (functional evolution), and adapt to new environments (experimental evolution). Together, these studies can help us better understand and respond to outbreaks.
What caused the sudden onset of severe congenital disease associated with Zika virus infections? Has the virus always been able to do this or is the virus now suddenly different? This topic has been hotly debated since the epidemic began (Grubaugh & Andersen, 2016). We recently cataloged many Zika virus mutations through our sequencing studies and will extensively test their fitness using in vitro and in vivo experiments. Combined with epidemiological information, we will use this data to help determine the role of Zika virus genetic factors associated with the epidemic. In a similar study, we found that a mutation in the ebola virus glycoprotein (A82V) arose early during the recent West Africa epidemic and enhanced infection in human cells, suggesting adaptation to human infection and/or transmission (Diehl et al., 2016). From the host’s side, we identified a novel human allele present in 1/3 of people with African ancestry that provides resistence to Plasmodium infection (Ma et al., 2018). We will continue to use this pipeline of field sequencing, identifying mutations of interest, and experimental fitness evaluation (i.e., functional evolution) to understand how other emerging mosquito-borne viruses, like Mayaro and Oropouche, may be changing in response to their environments.
Each project comes with their own set of challenges – e.g., harsh field conditions, sample degradation, mosquito manipulation, etc – and we are constantly searching for new approaches to overcome them. For example, we developed a method called “xenosurveillance” to detect human and animal pathogens in resource poor settings by collecting blood from recently fed mosquitoes, avoiding the need for direct blood draws by trained clinicians (Grubaugh et al., 2015). For laboratory studies, we developed a method to sequentially collect mosquito saliva from individual mosquitoes by exploiting their sugar feeding needs (see figure, Grubaugh et al., 2017), allowing us to track viral populations and more precisely measure the extrinsic incubation period. On a different front, due to the very low titers in clinical samples, many researchers were finding it difficult to sequence Zika virus, resulting in very limited data being released. We solved this issue by developing a highly multiplexed PCR approach to amplify the virus genome in many small pieces (i.e., “RNA jackhammering”), greatly enhancing our sequencing sensitivity (Quick et al., 2017). We are now using it as a cost-effective solution to sequence other viruses, such as West Nile and chikungunya, and have validated for use in measuring intrahost virus diversity (Grubaugh et al., 2019). We try not to be limited by what can be done with current technology and are always open to new approaches.