: Arthropod-borne viruses (arboviruses) are maintained in nature in cycles involving vertebrate hosts and hematophagous arthropods. Arboviruses can cause devastating diseases in vertebrate hosts, yet establish life-long persistent infections in vectors. The most amazing of arbovirus-vector interactions is transovarial transmission (TOT). LaCrosse (LAC) virus replicates in Aedes triseriatus mosquitoes during critical periods of vector oogenesis and embryogenesis without adverse effects. Co-regulation of vector and virus gene expression apparently modulates viral virulence in critical life stages of the vector. Although modulation of virulence is necessary, the arbovirus must also elude components of the vector innate immune response, e.g., apoptosis and RNAi, in order to persist. LAC (Bunyaviridae) and West Nile (WN, Flaviviridae) viruses induce apoptosis in vertebrate cells, but not in vector cells. Exogenously induced RNA interference (RNAi) inhibits both dengue (DEN; Flaviviridae) and LAC virus infection of mosquito cells, but we do not know if natural infections induce RNAi. In these studies, we will elucidate the roles of apoptosis and RNAi in arboviral persistence. LAC and WN virus will be used in comparative studies to elucidate whether apoptosis and RNAi are determinants of arbovirus attenuation and persistence in vectors. Both viruses induce apoptosis in vertebrate cells. LACV does not induce apoptosis in vector cells, is absolutely remarkable in its ability to establish long-term persistent infections in vectors, and is very efficiently transmitted TOT. WNV does not induce apoptosis in vector cells, establishes persistent infections in adult vectors, but is not transmitted TOT. The underlying hypothesis for these studies is that the replicative strategies of these two viruses determines their different phenotypes in vectors. RNAi and apoptosis can be triggered by dsRNA molecules. Replication and transcription of bunyaviruses differs fundamentally from that of flaviviruses; the dsRNA replicative intermediates of the two families differ dramatically, which could result in bunyavirus avoidance of both dsRNA-induced apoptosis and RNAi in vectors. Modern molecular biological and genomic approaches will be used to define the role of apoptosis and RNAi in persistent arbovirus infections in invertebrate hosts. Special emphasis will be devoted to determining the role of RNAi and apoptosis in TOT of arboviruses, which serves both to maintain trans-seasonally and to amplify bunyaviruses (but not flaviviruses) in nature. These studies may reveal fundamental molecular processes that condition these biologically and epidemiologically important vector phenotypes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI032543-13
Application #
7000346
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Costero, Adriana
Project Start
1992-03-01
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
13
Fiscal Year
2006
Total Cost
$247,788
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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
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
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
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

Showing the most recent 10 out of 25 publications