Overall we will continue studes of persistent infection and of the evolution of standard RNA virus and of D1 particles during long term persistence. We will continue to derive molecular clones of standard VSV, D1 particles and mutated virus from persistent infection. These will be used to help characterize and to sequence the biologically interesting mutants recovered from persistently infected cells. We will continue to isolate viral nucleocapsids from persistently infected cells and analyze these to gain insights into events occuring within persistently infected cells of all kinds. We will particularly be interested in ratios of viral to D1 nucleocapside, rates of synthesis, evidence for cyclic synthesis etc. In various types of persistence. We will continue our studies of persistently infected cells in vivo in nude mice, with specific emphasis upon the role of NK cells and interferon in rejection. We will continue our collaboraion with Drs. Reid and Bloom and colleagues at Albert Einstein Medical Center for these studies. We will determine the extent to which standard virus in persistent VSV infections is able to continue mutating to escape interference by the newly generated D1 particles arising after many years of persistence. The mechanisms of this escape from D1 particle interference will be explored by cross-protection studies matching various D1 particles and virus mutants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014627-20
Application #
3125818
Study Section
Virology Study Section (VR)
Project Start
1978-05-01
Project End
1988-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
20
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Novella, Isabel S; Gilbertson, Dorothy L; Borrego, Belen et al. (2005) Adaptability costs in immune escape variants of vesicular stomatitis virus. Virus Res 107:27-34
Weaver, S C; Brault, A C; Kang, W et al. (1999) Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells. J Virol 73:4316-26
Novella, I S; Hershey, C L; Escarmis, C et al. (1999) Lack of evolutionary stasis during alternating replication of an arbovirus in insect and mammalian cells. J Mol Biol 287:459-65
Novella, I S; Quer, J; Domingo, E et al. (1999) Exponential fitness gains of RNA virus populations are limited by bottleneck effects. J Virol 73:1668-71
Holland, J; Domingo, E (1998) Origin and evolution of viruses. Virus Genes 16:13-21
Domingo, E; Holland, J J (1997) RNA virus mutations and fitness for survival. Annu Rev Microbiol 51:151-78
Novella, I S; Cilnis, M; Elena, S F et al. (1996) Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance. J Virol 70:6414-7
Quer, J; Huerta, R; Novella, I S et al. (1996) Reproducible nonlinear population dynamics and critical points during replicative competitions of RNA virus quasispecies. J Mol Biol 264:465-71
Domingo, E; Escarmis, C; Sevilla, N et al. (1996) Basic concepts in RNA virus evolution. FASEB J 10:859-64
Novella, I S; Elena, S F; Moya, A et al. (1996) Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift. Mol Gen Genet 252:733-8

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