Investigations of the evolutionary, epidemic, and maintenance potential of La Crosse virus
Date
2008
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Abstract
Arthropod-borne viruses are resurging and emerging worldwide, and La Crosse virus (LACV) is a prototypical emergent virus in the United States. In this dissertation, the evolutionary, epidemic, and maintenance potential of LACV is investigated. In laboratory and field studies, LACV has shown significant evolutionary and epidemic potential through point mutations and segment reassortment. Through sensitive molecular epidemiological techniques, significant genetic variation was observed in LACV RNA amplified from field-infected Aedes triseriatus mosquitoes, suggesting the potential for frequent segment reassortment of LACV in nature. Maximum parsimony phylogenetic analysis and linkage disequilibrium analysis revealed that 25-38.6% of the mosquito samples contained reassortant viruses. The geographical, environmental and temporal factors that condition the genetic structure of LACV were also investigated. The analysis revealed that there are no physical barriers to viral flow in the study site, indicating that the more virulent LACV strains could traffic and be transmitted throughout the entire 15,360 km2 study range (southeastern Wisconsin, southwestern Minnesota and northeastern Iowa). Although there were no barriers to viral gene flow and no isolation by distance, a significant temporal association with viral genotype was revealed. The maintenance of LACV in nature is not well understood. Mathematical models have revealed that field infection rates are well below those required to maintain the virus in nature. However, the mathematical models have not considered the possibilities of stably-infected Ae. triseriatus mosquitoes or a LACV induced mating advantage for infected females. Super-infected Ae. triseriatus mosquitoes in nature were identified in southeastern Wisconsin and southwestern Minnesota in these studies (0.011% prevalence rate) suggesting that LACV could be maintained in nature through a stabilized infection in a small number of females. LACV maintenance in nature may also be assisted by a mating advantage for Ae. triseriatus females infected with LACV. In this study, LACV transovarially-infected female mosquitoes become inseminated faster than uninfected mosquitoes, and this could increase the chance for transovarial transmission as well as venereal transmission of the virus. The evolutionary and maintenance potential of LACV was investigated in this dissertation and the results provide insight into the determinants of arbovirus emergence and epidemic potential in nature.
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Subject
Aedes triseriatus
La Crosse virus
maintenance potential
phylogeny
super infection
molecular biology
virology
epidemiology