The nucleotide sequence at the recombination/integration sites of the hybrid viruses Ad2 +ND3 and Ad2 +ND5

The nucleotide sequence at the recombination/integration sites of the adenovirus 2-simian virus 40 hybrid viruses, Ad2 +ND3 and Ad2 +ND5, is reported. These viruses were obtained by passages through human cells and fail to express the SV40-related proteins. The lack of expression of SV40-related proteins has been explained on the basis of the nucleotide sequence at the recombination sites. Ad2 +ND3 has the entire reading frame for the SV40T antigen removed up to the translation termination codon. The recombination event in Ad2 +ND5 was found to occur in the leader region 11 nucleotides upstream from the splice junction, thus totally eliminating the naturally occurring splice site, which might have lead to defective processing of the mRNA. Alternatively, because of the large deletion, this virus is incapable of making similar hybrid proteins as in Ad2 +ND1, Ad2 +ND2, and Ad2 +ND4, which share the N-terminal sequence of the 16-kDa glycoprotein of the wild-type virus. Thus, either one or both of these events may explain the lack of synthesis of the SV40 T antigen specific protein. Ad2 +ND3 and Ad2 +ND5 share the sequences at the right junction which suggests their origin from a common precursor. Also, the recombination was found to result in the disruption of the poly (A) addition signal of the adenovirus 2 early region III transcripts. All of the junction sequences were found to be rich in A:T base pairs.