We are investigating several aspects of the structure and replication of enveloped RNA viruses. A major objective is to determine what differences in the amino acid sequence of related glycoproteins (G proteins) from vesicular stomatitis virus (VSV) account for the differences in their requirement for oligosaccharides. The nonglycosylated G proteins of VSV are temperature-sensitive but the degree of sensitivity depends on the amino acid sequence of the protein. Differences in amino acids will be inferred from sequencing of cDNAs derived from the mRNAs for the related glycoproteins. We are also studying defective-interfering (DI) particles of Sindbis virus and plan to continue the characterization of the defective RNA. To this end we are sequencing several DI RNAs to identify those sequences which are conserved in all DI RNAs and would be considered essential for their ability to interfere with the replication of standard virus and for them to be packaged successfully. An important goal in this work is to examine the role of both DI particles and the standard virus in establishing and maintaining persistent infections in cultured cells. In vitro models of persistent infections should lead to the development of methods for detecting low levels of virus replication and for determining the presence or absence of defective nucleic acids. An understanding of how viruses can persist in cells can provide directions to be explored in determining their putative role in disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI011377-13
Application #
3444442
Study Section
Virology Study Section (VR)
Project Start
1978-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Schlesinger, S (2000) Alphavirus expression vectors. Adv Virus Res 55:565-77
Polo, J M; Belli, B A; Driver, D A et al. (1999) Stable alphavirus packaging cell lines for Sindbis virus and Semliki Forest virus-derived vectors. Proc Natl Acad Sci U S A 96:4598-603
Frolov, I; Agapov, E; Hoffman Jr, T A et al. (1999) Selection of RNA replicons capable of persistent noncytopathic replication in mammalian cells. J Virol 73:3854-65
Ivanova, L; Schlesinger, S; Olivo, P D (1999) Regulated expression of a Sindbis virus replicon by herpesvirus promoters. J Virol 73:1998-2005
Olivo, P D; Collins, P L; Peeples, M E et al. (1998) Detection and quantitation of human respiratory syncytial virus (RSV) using minigenome cDNA and a Sindbis virus replicon: a prototype assay for negative-strand RNA viruses. Virology 251:198-205
Agapov, E V; Frolov, I; Lindenbach, B D et al. (1998) Noncytopathic Sindbis virus RNA vectors for heterologous gene expression. Proc Natl Acad Sci U S A 95:12989-94
Frolov, I; Frolova, E; Schlesinger, S (1997) Sindbis virus replicons and Sindbis virus: assembly of chimeras and of particles deficient in virus RNA. J Virol 71:2819-29
Frolova, E; Frolov, I; Schlesinger, S (1997) Packaging signals in alphaviruses. J Virol 71:248-58
Dryga, S A; Dryga, O A; Schlesinger, S (1997) Identification of mutations in a Sindbis virus variant able to establish persistent infection in BHK cells: the importance of a mutation in the nsP2 gene. Virology 228:74-83
Frolov, I; Schlesinger, S (1996) Translation of Sindbis virus mRNA: analysis of sequences downstream of the initiating AUG codon that enhance translation. J Virol 70:1182-90

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