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.
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