LaCrosse encephalitis virus (LAC) remains a major cause of pediatric encephalitis in children in the United States. The goal of this research project is to determine how the virus is maintained and amplified in its mosquito vector. Virus and vector genetic determinants of efficient transovarial transmission (TOT) and maintenance of LAC virus in Aedes triseriatus mosquitoes will be determined. We previously demonstrated that LAC virus scavenges caps and 5' nucleotide sequences from host mRNA to prime its own transcription, and thus ongoing host transcription is required for virus replication. In mosquitoes and mosquito cells this the co- regulation of host and virus transcription modulates deleterious effects of virus replication and promotes virus overwintering. In the proposed studies, the molecular bases and molecular biological determinants of LAC virus cap scavenging will be delineated. Vector and virus phylogenetic relationships that condition coregulation of vector and virus transcription and efficient TOT and overwintering of bunyaviruses will be elucidated. Finally, host genes that express donor mRNAs for cap scavenging during critical periods of vector-virus interactions will be revealed. Two such host mRNAs have been identified; one of which predominantly donates caps during persistent infections of cells and one which predominates during diapause. These genes, which are potential genetic determinants of biologically and epidemiologically important vector phenotypes, will be identified and characterized molecularly and biologically. The proposed studies will provide a more basic understanding of mechanisms that maintain bunyavirus cycle integrity in nature and factors that promote and constrain arbovirus evolution and emergence. The studies will also potentially provide fundamental information on molecular genetic determinants of important vector phenotypes (eg - diapause) and vector-pathogen interactions (eg -attenuation). The studies may also delineate molecular markers for diapause induction and release in vectors, which would be a significant contribution to the field of vector biology. Overall the proposed studies will provide new information on vector-pathogen interactions that may lead to new control strategies for vector borne diseases and may provide new insights into the epidemic potential of these important pathogens.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Special Emphasis Panel (ZRG5-TMP (01))
Program Officer
Meegan, James M
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Colorado State University-Fort Collins
Schools of Veterinary Medicine
Fort Collins
United States
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Reese, Sara M; Mossel, Eric C; Beaty, Meaghan K et al. (2010) Identification of super-infected Aedes triseriatus mosquitoes collected as eggs from the field and partial characterization of the infecting La Crosse viruses. Virol J 7:76
Beck, Eric T; Lozano Fuentes, Saul; Geske, David A et al. (2009) Patterns of variation in the inhibitor of apoptosis 1 gene of Aedes triseriatus, a transovarial vector of La Crosse virus. J Mol Evol 68:403-13
Reese, Sara M; Beaty, Meaghan K; Gabitzsch, Elizabeth S et al. (2009) Aedes triseriatus females transovarially infected with La Crosse virus mate more efficiently than uninfected mosquitoes. J Med Entomol 46:1152-8
Reese, Sara M; Blitvich, Bradley J; Blair, Carol D et al. (2008) Potential for La Crosse virus segment reassortment in nature. Virol J 5:164
Wang, Hua; Blair, Carol D; Olson, Ken E et al. (2008) Effects of inducing or inhibiting apoptosis on Sindbis virus replication in mosquito cells. J Gen Virol 89:2651-61
Bryant, Bart; Blair, Carol D; Olson, Ken E et al. (2008) Annotation and expression profiling of apoptosis-related genes in the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 38:331-45
Li, Q; Li, H; Blitvich, B J et al. (2007) The Aedes albopictus inhibitor of apoptosis 1 gene protects vertebrate cells from bluetongue virus-induced apoptosis. Insect Mol Biol 16:93-105
Beck, Eric T; Blair, Carol D; Black 4th, William C et al. (2007) Alternative splicing generates multiple transcripts of the inhibitor of apoptosis protein 1 in Aedes and Culex spp. mosquitoes. Insect Biochem Mol Biol 37:1222-33
Blakqori, Gjon; Delhaye, Sophie; Habjan, Matthias et al. (2007) La Crosse bunyavirus nonstructural protein NSs serves to suppress the type I interferon system of mammalian hosts. J Virol 81:4991-9
Gabitzsch, E S; Blair, C D; Beaty, B J (2006) Effect of La Crosse virus infection on insemination rates in female Aedes triseriatus (Diptera: Culicidae). J Med Entomol 43:850-2

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