Abstract

The rhabdovirus virus, vesicular stomatic virus is a prototype negative strand RNA virus and other members of the Mononegavirales are serious human and animal pathogens.
The aims of the proposal are to examine, both at the level of their primary nucleotide sequence and higher order structure, the cis- acting signals in the RNA genome of VSV that regulate individual steps in viral replication. Specifically it is proposed: 1. To analyze the role of primary RNA sequence and complementarily of the VSV genomic termini in controlling encapsidation, polymerase binding and RNA replication; 2. To analyze the role of primary RNA sequence and the leader RNA in influencing the decision of the polymerase at the leader-N junction to transcribe or replicate; 3. To define primary RNA sequence and higher-order structural elements at the intercistronic junctions that control the generation of discrete capped and polyadenylated mRNAs; 4. To analyze the cis-acting sequences required for assembly of replicated RNAs into infectious virus particles; 5. To analyze trans-acting factors in the control of transcription and replication; 6. To develop VSV as a vector for gene expression and delivery; 7. To perform high-resolution structural analyses of VSV N:P protein complexes, nucleocapsids and virions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI012464-25
Application #
6169362
Study Section
Special Emphasis Panel (ZRG5-VR (01))
Program Officer
Meegan, James M
Project Start
1987-04-01
Project End
2001-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
25
Fiscal Year
2000
Total Cost
$332,186
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Mondal, Arindam; Victor, Ken G; Pudupakam, R S et al. (2014) Newly identified phosphorylation site in the vesicular stomatitis virus P protein is required for viral RNA synthesis. J Virol 88:1461-72
Harouaka, Djamila; Wertz, Gail W (2012) Second-site mutations selected in transcriptional regulatory sequences compensate for engineered mutations in the vesicular stomatitis virus nucleocapsid protein. J Virol 86:11266-75
Rainsford, Edward W; Harouaka, Djamila; Wertz, Gail W (2010) Importance of hydrogen bond contacts between the N protein and RNA genome of vesicular stomatitis virus in encapsidation and RNA synthesis. J Virol 84:1741-51
Harouaka, Djamila; Wertz, Gail W (2009) Mutations in the C-terminal loop of the nucleocapsid protein affect vesicular stomatitis virus RNA replication and transcription differentially. J Virol 83:11429-39
Galloway, Summer E; Wertz, Gail W (2009) A temperature sensitive VSV identifies L protein residues that affect transcription but not replication. Virology 388:286-93
Hinzman, Edward E; Barr, John N; Wertz, Gail W (2008) Selection for gene junction sequences important for VSV transcription. Virology 380:379-87
Galloway, Summer E; Wertz, Gail W (2008) S-adenosyl homocysteine-induced hyperpolyadenylation of vesicular stomatitis virus mRNA requires the methyltransferase activity of L protein. J Virol 82:12280-90
Barr, John N (2007) Bunyavirus mRNA synthesis is coupled to translation to prevent premature transcription termination. RNA 13:731-6
Green, Todd J; Zhang, Xin; Wertz, Gail W et al. (2006) Structure of the vesicular stomatitis virus nucleoprotein-RNA complex. Science 313:357-60
Martinez, Isidoro; Wertz, Gail W (2005) Biological differences between vesicular stomatitis virus Indiana and New Jersey serotype glycoproteins: identification of amino acid residues modulating pH-dependent infectivity. J Virol 79:3578-85

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