Host range and cell cycle activation properties of polyomavirus large T-antigen mutants defective in pRB binding

Journal Article · Tue Nov 01 04:00:00 EST 1994 · Journal of Virology

OSTI ID:153480

Freund, R ^[1]; Bauer, P H; Benjamin, T L ^[2]; Crissman, H A ^[3]; Bradbury, E M ^[3]

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1. Univ. of Maryland School of Medicine, Baltimore, MD (United States). Dept. of Microbiology and Immunology
2. Harvard Medical School, Boston, MA (United States). Dept. of Pathology
3. Los Alamos National Labs., NM (United States)

The authors have examined the growth properties of polyomavirus large T-antigen mutants that ar unable to bind pRB, the product of the retinoblastoma tumor suppressor gene. These mutants grow poorly on primary mouse cells yet grow well on NIH 3T3 and other established mouse cell lines. Preinfection of primary baby mouse kidney (BMK) epithelial cells with wild-type simian virus 40 renders these cells permissive to growth of pRB-binding polyomavirus mutants. Conversely, NIH 3T3 cells transfected by and expressing wild-type human pRB become nonpermissive. Primary fibroblasts for mouse embryos that carry a homozygous knockout of the RB gene are permissive, while those from normal littermates are nonpermissive. The host range of polyomavirus pRB-binding mutants is thus determined by expression or lack of expression of functional pRB by the host. These results demonstrate the importance of pRB binding by large T antigen for productive viral infection in primary cells. Failure of pRB-binding mutants to grow well in BMK cells correlates with their failure to induce progression from G{sub 0} or G{sub 1} through the S phase of the cell cycle. Time course studies show delayed synthesis and lower levels of accumulation of large T antigen, viral DNA, and VP1 in mutant compared with wild-type virus-infected BMK cells. These results support a model in which productive infection by polyomavirus in normal mouse cells is tightly coupled to the induction and progression of the cell cycle. 48 refs., 6 figs., 5 tabs.

• OSTI ID: 153480
• Journal Information: Journal of Virology, Journal Name: Journal of Virology Journal Issue: 11 Vol. 68; ISSN JOVIAM; ISSN 0022-538X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
ANTIGENS
BIOCHEMICAL REACTION KINETICS
CELL CYCLE
CELL TRANSFORMATIONS
DNA REPLICATION
EPITHELIUM
ETIOLOGY
EXPERIMENTAL DATA
GENE MUTATIONS
GENE REGULATION
GENES
MICE
VIRAL DISEASES
VIRUSES