The alphavirus group consists of about 20 viruses, many of which are important human veterinary pathogens. We will continue our study of the molecular biology of alphavirus replication in several ways. We have constructed a complete cloned DNA copy of the Sindbis virus RNA and are developing techniques to rapidly construct cloned DNA copies inserted next to promoter sequences or restriction sites. We will attempt to obtain infectious RNA from such cloned copies which would in turn allow numerous experiments which probe the replication strategy of this virus. We have completely sequenced the genome of Sindbis virus, 11703 nucleotides in length, and will map all of the proteins encoded in this RNA to the RNA nucleotide sequence. We will also continue comparative studies of alphaviruses to study their evolution. We have initiated studies of a second group of Togaviruses, the flaviviruses, which contain about 60 members of which many are important human pathogens. We intend to sequence the structural proteins of the vaccine strain of yellow fever virus by a combination of nucleotide sequencing and protein sequencing in order to probe the replication strategy of these viruses and to obtain comparative sequence data on several flaviviruses to study their evolution. Both alphaviruses and flaviviruses alternate in nature between growth in arthropod vectors (mosquitoes or ticks) and growth in vertebrates and studies of strain divergences are of particular interest.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI020612-04
Application #
3444665
Study Section
Experimental Virology Study Section (EVR)
Project Start
1984-03-01
Project End
1989-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Mukhopadhyay, Suchetana; Zhang, Wei; Gabler, Stefan et al. (2006) Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses. Structure 14:63-73
Kim, Kyongmin Hwang; Rumenapf, Tillmann; Strauss, Ellen G et al. (2004) Regulation of Semliki Forest virus RNA replication: a model for the control of alphavirus pathogenesis in invertebrate hosts. Virology 323:153-63
Rossmann, Michael G (2003) John Edsall's influence. Biophys Chem 100:105-8
Strauss, Ellen G; Lenches, Edith M; Strauss, James H (2002) Molecular genetic evidence that the hydrophobic anchors of glycoproteins E2 and E1 interact during assembly of alphaviruses. J Virol 76:10188-94
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Zhang, Wei; Fisher, Bonnie R; Olson, Norman H et al. (2002) Aura virus structure suggests that the T=4 organization is a fundamental property of viral structural proteins. J Virol 76:7239-46
Heil, M L; Albee, A; Strauss, J H et al. (2001) An amino acid substitution in the coding region of the E2 glycoprotein adapts Ross River virus to utilize heparan sulfate as an attachment moiety. J Virol 75:6303-9
Kim, K H; Strauss, E G; Strauss, J H (2000) Adaptive mutations in Sindbis virus E2 and Ross River virus E1 that allow efficient budding of chimeric viruses. J Virol 74:2663-70
van Der Most, R G; Murali-Krishna, K; Ahmed, R et al. (2000) Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of the dengue virus-specific CD8 T-cell response. J Virol 74:8094-101
van der Most, R G; Corver, J; Strauss, J H (1999) Mutagenesis of the RGD motif in the yellow fever virus 17D envelope protein. Virology 265:83-95

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