E1A ONCOGENE OF ADENOVIRUS-12 MEDIATES TRANSREPRESSION OF MHC CLASS-ITRANSCRIPTION IN AD5 AD12 SOMATIC HYBRID TRANSFORMED-CELLS/

Reduction of the Major Histocompatibility Complex (MHC) class I antige ns on the surface of adenovirus type 12 (Ad12) transformed cells is th ought to contribute to their tumorigenic potential. The E1A gene of Ad 12 mediates this effect by repressing the MHC class I transcriptional enhancer. By contrast, Ad5-transformed cells are not blocked in class I gene expression and are nontumorigenic. Because E1A proteins modulat e transcription by interacting with several different cellular factors , we inquired whether the Ad5 E1A proteins could interfere with the ab ility of Ad12 E1A proteins to repress class 1 transcription. Somatic c ell hybrids, produced by fusing Ad5- and Ad12-transformed cells, expre ssed E1A proteins of both virus serotypes. The level of class expressi on and transcription in the 5/12 hybrid cell lines was reduced to the same degree as in the original Ad12-transformed cells. Also observed i n the 5/12 hybrid cell lines was strong binding activity to the R2 sub element of the H-2 class I enhancer which, in Ad12-transformed cells, correlates with repression of class I transcription. These results dem onstrate that Ad 12 E1A proteins mediate repression of the class I enh ancer through a mechanism that is unaffected by Ad5 E1A proteins. (C) 1994 Academic Press, Inc.