The Nodaviridae are a family of small icosahedral viruses with bipartite, single-stranded, positive-sense RNA genomes. Containing only 4.5 kb, their genomes are among the smallest and simplest of all known animal viruses, yet they replicate up to 100-fold more abundantly than most other viral RNAs, and can do so in cells from vertebrates, insects, and even plants. These and other features of the nodaviruses allow steps in their replication cycles to be examined at levels of resolution that cannot yet be achieved with other animal viruses. The advances in our basic understanding of the dynamic RNA-protein interactions involved in nodavirus replication can be confidently expected to illuminate the study of the many positive-strand RNA viruses with medical and economic importance. Moreover, because of the simplicity, robustness, and extraordinary amplifying power of the nodavirus RNA replicases, they are promising candidates for development as components of expression vectors for a wide range of applications. The work described in this proposal focuses on three aspects of the molecular biology of the nodaviruses. The first is a detailed study of the mechanism of RNA replication that combines genetic and biochemical approaches to examine the interactions of the RNA replicase with its templates; the possibility that components of the cellular splicing machinery are involved in RNA replication; and the properties of the RNA replicase and other enzymes that mediate replication. The second addresses how virus assembly and disassembly occur, focusing on the functions of the RNA encapsidation signals and exploiting the ability to carry out both the disassembly and assembly of infectious virus in a cell-free system. The third explores how RNA replication can be harnessed most effectively to drive the amplification and expression of heterologous RNAs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018270-20
Application #
6169402
Study Section
Virology Study Section (VR)
Program Officer
Meegan, James M
Project Start
1987-08-01
Project End
2002-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
20
Fiscal Year
2000
Total Cost
$351,292
Indirect Cost
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
Price, B Duane; Eckerle, Lance D; Ball, L Andrew et al. (2005) Nodamura virus RNA replication in Saccharomyces cerevisiae: heterologous gene expression allows replication-dependent colony formation. J Virol 79:495-502
Novella, Isabel S; Ball, L Andrew; Wertz, Gail W (2004) Fitness analyses of vesicular stomatitis strains with rearranged genomes reveal replicative disadvantages. J Virol 78:9837-41
Johnson, Karyn N; Tang, Liang; Johnson, John E et al. (2004) Heterologous RNA encapsidated in Pariacoto virus-like particles forms a dodecahedral cage similar to genomic RNA in wild-type virions. J Virol 78:11371-8
Johnson, Kyle L; Price, B Duane; Eckerle, Lance D et al. (2004) Nodamura virus nonstructural protein B2 can enhance viral RNA accumulation in both mammalian and insect cells. J Virol 78:6698-704
Pringle, Fiona M; Johnson, Karyn N; Goodman, Cynthia L et al. (2003) Providence virus: a new member of the Tetraviridae that infects cultured insect cells. Virology 306:359-70
Albarino, Cesar G; Eckerle, Lance D; Ball, L Andrew (2003) The cis-acting replication signal at the 3' end of Flock House virus RNA2 is RNA3-dependent. Virology 311:181-91
Johnson, Kyle L; Price, B Duane; Ball, L Andrew (2003) Recovery of infectivity from cDNA clones of nodamura virus and identification of small nonstructural proteins. Virology 305:436-51
Eckerle, Lance D; Albarino, Cesar G; Ball, L Andrew (2003) Flock House virus subgenomic RNA3 is replicated and its replication correlates with transactivation of RNA2. Virology 317:95-108
Johnson, Karyn N; Ball, L Andrew (2003) Virions of Pariacoto virus contain a minor protein translated from the second AUG codon of the capsid protein open reading frame. J Gen Virol 84:2847-52
Price, B D; Ahlquist, P; Ball, L A (2002) DNA-directed expression of an animal virus RNA for replication-dependent colony formation in Saccharomyces cerevisiae. J Virol 76:1610-6

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