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Titolo:
CONSTRUCTING CHIMERIC TYPE-12 TYPE-5 ADENOVIRUS E1A GENES AND USING THEM TO IDENTIFY AN ONCOGENIC DETERMINANT OF ADENOVIRUS-TYPE-12/
Autore:
TELLING GC; WILLIAMS J;
Indirizzi:
CARNEGIE MELLON UNIV,DEPT BIOL SCI,4400 5TH AVE PITTSBURGH PA 15213 CARNEGIE MELLON UNIV,DEPT BIOL SCI PITTSBURGH PA 15213
Titolo Testata:
Journal of virology
fascicolo: 2, volume: 68, anno: 1994,
pagine: 877 - 887
SICI:
0022-538X(1994)68:2<877:CCTTAE>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSFORMED RAT-CELLS; TOXIC LYMPHOCYTES-T; HOST-RANGE MUTANTS; SPLICED MESSENGER-RNAS; NATURAL-KILLER CELLS; EARLY VIRAL GENES; HUMAN CYCLIN-A; CLASS-I GENE; FUNCTIONAL DOMAINS; EARLY REGION-1A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
85
Recensione:
Indirizzi per estratti:
Citazione:
G.C. Telling e J. Williams, "CONSTRUCTING CHIMERIC TYPE-12 TYPE-5 ADENOVIRUS E1A GENES AND USING THEM TO IDENTIFY AN ONCOGENIC DETERMINANT OF ADENOVIRUS-TYPE-12/", Journal of virology, 68(2), 1994, pp. 877-887

Abstract

The E1A gene of highly oncogenic type 12 adenovirus (Ad12) possesses a segment unique to this serotype and comprising 60 base pairs contiguous with and separating conserved regions 2 and 3 in the gene. A similar but slightly longer segment is also present in the E1A gene of highly oncogenic simian adenovirus type 7 (D. Kimelman, J. S. Miller, D. Porter, and B. E. Roberts, J. Virol. 53:399-409, 1985). This segment ismissing entirely from the E1A gene of type 5 adenovirus, which is nononcogenic. To test the hypothesis that this unique separating or ''spacer'' region influences the oncogenicity of Ad12, we constructed ClaI and SmaI restriction sites on either side of it, which allowed reciprocal exchange between this and the equivalent cassette from type 5 adenovirus E1A, bounded by the same restriction sites intrinsic to that gene. The resultant Ad12-based chimeric viruses, ch702 and ch704, in which the spacer region is replaced with (in-frame) type 5 sequence, grownormally on human A549 cells and display wild-type transformation frequencies on baby rat and mouse kidney cells. In contrast, the oncogenic capacity of these chimeric viruses, as measured by tumor induction following virus inoculation in Hooded Lister rats, is greatly reduced. Likewise, cells transformed by ch702 and ch704 display reduced tumorigenicity compared with wild-type transformants in syngeneic rats. Theseresults, coupled with recent preliminary tests using a mutant with a point mutation in this region, support the view that the unique spacerregion of type 12 is an oncogenic determinant of this virus.

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Documento generato il 30/11/20 alle ore 09:30:12