The tissue specificity of both DNA replication and gene expression of Polyomavirus is to be studied in both in vitro and in vivo systems including infected mice. An emphasis will be to utilize homologous recombinant constructs so that cis interactions between the overlapping regulatory elements might be analyzed. The initial effort will be towards understanding the function of the Pvu II-4 region (N 5128 to 5262) in regulating tissue specificity. We have recently established that this element exerts both a negative (repressing) as well as positive (enhancing) regulatory effect in a tissue specific manner. The mechanism of this observation will be studied. The in vivo tissue specificity of these viable recombinants will then be compared to the specificity seen with trangenic mice to determine if the phenotype of the cis regulatory elements is independent of development and of chromosomal location. Finally, we will investigate the genetic determinants of papovirus species (as opposed to tissue) specific DNA replication. Using recombinants of SV40 and Polyoma virus, DNA regulation in both primate and murine cells will be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM036605-01
Application #
3290921
Study Section
Virology Study Section (VR)
Project Start
1986-04-01
Project End
1991-03-30
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Villarreal, L P; Defilippis, V R; Gottlieb, K A (2000) Acute and persistent viral life strategies and their relationship to emerging diseases. Virology 272:6-Jan
Gottlieb, K; Villarreal, L P (2000) The distribution and kinetics of polyomavirus in lungs of intranasally infected newborn mice. Virology 266:52-65
Piatti, P G; Gottlieb, K A; Taylor, J A et al. (1998) Approaches to study interactions between small DNA viruses and differentiated tissue. Methods 16:62-82
You, Z; Villarreal, L P (1996) Mapping of polyomavirus DNA replicative intermediates by two-dimensional gel analysis using chemiluminescent detection. J Virol Methods 56:173-8
Atencio, I A; Belli, B; Hobbs, M et al. (1995) A model for mixed virus disease: co-infection with Moloney murine leukemia virus potentiates runting induced by polyomavirus (A2 strain) in Balb/c and NIH Swiss mice. Virology 212:356-66
Shadan, F F; Villarreal, L P (1995) The evolution of small DNA viruses of eukaryotes: past and present considerations. Virus Genes 11:239-57
Shadan, F F; Cowsert, L M; Villarreal, L P (1994) n-Butyrate, a cell cycle blocker, inhibits the replication of polyomaviruses and papillomaviruses but not that of adenoviruses and herpesviruses. J Virol 68:4785-96
Atencio, I A; Meraz, A; Villarreal, L P (1994) The secretory cells of mouse salivary glands are nonpermissive for polyomavirus replication. Virology 200:842-8
Atencio, I A; Villarreal, L P (1994) Polyomavirus replicates in differentiating but not in proliferating tubules of adult mouse polycystic kidneys. Virology 201:26-35
Atencio, I A; Shadan, F F; Zhou, X J et al. (1993) Adult mouse kidneys become permissive to acute polyomavirus infection and reactivate persistent infections in response to cellular damage and regeneration. J Virol 67:1424-32

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