The alphaviruses and flaviviruses are two groups of mosquito-borne viruses cause many cases of human illness each year. We wish to understand the molecular biology of the replication of these two groups of viruses in great detail and to explore the evolution of these viruses.
Three specific aims are proposed in this renewal application. (1) To identify and characterize the cellular receptor to which alphaviruses attach in the primary process of infection. Alphaviruses have a broad phylogenetic host range, replicating in anthropods (mosquitoes) as well as in higher vertebrates, and the distribution of cellular receptors and the possible involvement of receptors in tissue tropism and virulence will be explored. (2) To explore the interactions of the nucleocapsid and envelope glycoproteins of alphaviruses with one another during the maturation of alphaviruses. Site specific mutagenesis will be used to examine domains of capsid and domains of glycoproteins that have been implicated in previous results as important in these interactions. Second site revertants of site specific mutants may also be useful in defining domains that interact. (3) To determine the translation strategy and processing mechanisms used to product flavivirus proteins. From sequencing data both virus encoded and cellular proteases have been invoked in processing of a very large precursor flavivirus polyprotein. Translation of RNAs derived from cDNA constructs in vivo or in vitro will be used in these studies.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Unknown (R22)
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Virology Study Section (VR)
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California Institute of Technology
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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
Kuhn, Richard J; Zhang, Wei; Rossmann, Michael G et al. (2002) Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell 108:717-25
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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