A MUTANT OF CANINE ADENOVIRUS TYPE-2 WITH A DUPLICATION OF THE E1A REGION EXHIBITS ALTERED EXPRESSION OF EARLY REGION-4

The genomic DNA of a vaccine strain of canine adenovirus type 2 (Vaxitas; ICI Tasman) has been shown to contain two copies of the E1a region, the second being at the far right end of the genome. DNA sequence analysis of the right terminal 2.8 kbp of this vaccine strain showed that numerous point mutations have occurred in the second copy, which would preclude the synthesis of any functional products. However, expression vectors in which the E1a promoter from the right terminus were linked to the chloramphenicol acetyltransferase gene showed that the promoter was fully functional. Furthermore, the activity of the reiterated E1a promoter was considerably greater than that of the normal E4 promoter. This dramatic change in the regulation of E4 expression may be an important factor in determining the altered host cell specificity displayed by this vaccine strain virus.