Abstract

We plan a systematic, detailed comparative study of the mechanism of replication of the RNA genomes of two different negative strand viruses, vesicular stomatitis virus (VSV), a rhabdovirus and Sendai virus, a paramyxovirus. We will carry out these studies with the use of an in vitro reconstitution assay for RNA genome replication that we have recently developed, utilizing nucleocapsids derived from either the defective interfering particles of each virus or the wild type viruses as templates. We shall determine if the requirements for initiation are the same as those for elongation during RNA replication. For each virus we shall identify and purify the individual viral proteins required for the various steps of RNA replication and encapsidation. We also propose to develop an assay by which we can identify and purify any host cell factors which may be involved specifically in the replication of the RNA genomes of these viruses. We plan to select hybridomas secreting monoclonal antibodies to the VSV and Sendai nucleocapsid proteins, and also to isolate and use amber mutants in these proteins, as approaches to understanding the specific functions of the individual viral nucleocapsid proteins in RNA replication.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014594-08
Application #
3125806
Study Section
Experimental Virology Study Section (EVR)
Project Start
1978-06-01
Project End
1989-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Cevik, Bayram; Smallwood, Sherin; Moyer, Sue A (2007) Two N-terminal regions of the Sendai virus L RNA polymerase protein participate in oligomerization. Virology 363:189-97
Grdzelishvili, Valery Z; Smallwood, Sherin; Tower, Dallas et al. (2006) Identification of a new region in the vesicular stomatitis virus L polymerase protein which is essential for mRNA cap methylation. Virology 350:394-405
Thai, To-Ha; Kearney, John F (2005) Isoforms of terminal deoxynucleotidyltransferase: developmental aspects and function. Adv Immunol 86:113-36
Grdzelishvili, Valery Z; Smallwood, Sherin; Tower, Dallas et al. (2005) A single amino acid change in the L-polymerase protein of vesicular stomatitis virus completely abolishes viral mRNA cap methylation. J Virol 79:7327-37
Cevik, Bayram; Holmes, David E; Vrotsos, Emmanuel et al. (2004) The phosphoprotein (P) and L binding sites reside in the N-terminus of the L subunit of the measles virus RNA polymerase. Virology 327:297-306
Cevik, Bayram; Kaesberg, Jeffrey; Smallwood, Sherin et al. (2004) Mapping the phosphoprotein binding site on Sendai virus NP protein assembled into nucleocapsids. Virology 325:216-24
Smallwood, Sherin; Moyer, Sue A (2004) The L polymerase protein of parainfluenza virus 3 forms an oligomer and can interact with the heterologous Sendai virus L, P and C proteins. Virology 318:439-50
Cevik, Bayram; Smallwood, Sherin; Moyer, Sue A (2003) The L-L oligomerization domain resides at the very N-terminus of the sendai virus L RNA polymerase protein. Virology 313:525-36
Tuckis, Jeffery; Smallwood, Sherin; Feller, Joyce A et al. (2002) The C-terminal 88 amino acids of the Sendai virus P protein have multiple functions separable by mutation. J Virol 76:68-77
Smallwood, Sherin; Cevik, Bayram; Moyer, Sue A (2002) Intragenic complementation and oligomerization of the L subunit of the sendai virus RNA polymerase. Virology 304:235-45

Showing the most recent 10 out of 34 publications