19-kDa tumor antigen coded by early region E1b of adenovirus 2 is required for efficient synthesis and for protection of viral DNA.
The adenovirus E1b region (mp 4.5-11.2) codes for two major tumor antigens of 53 and 19 kDa. The lp+ locus maps within the 19-kDa tumor antigen-coding region and has been shown to play an essential role in cell transformation. We have investigated the role of the 19-kDa tumor antigen during productive virus growth using a specific Ad2 mutant (dl250) lacking most of the 19-kDa tumor antigen-coding region. Mutant dl250 grows more slowly and yields about 100-fold less progeny virus than Ad2 wt in human KB cells. In cells infected with mutant dl250, viral DNA is present at only about one-half the level of that of Ad2 wt. The defect in DNA accumulation appears to be both at the level of DNA synthesis and stability of newly synthesized DNA. In mutant-infected cells, newly replicated viral as well as cellular DNA are extensively degraded during late stages of viral infection. We have mapped a class of Ad12 (highly oncogenic group A) mutants (cyt) that are nononcogenic in newborn hamsters and induce DNA degradation to the 19-kDa tumor antigen-coding region by intertypic complementation analysis. These results strongly suggest that the 19-kDa tumor antigen plays an essential role in efficient viral DNA synthesis and protection of newly replicated viral DNA against cellular nucleases in addition to its role in cell transformation and tumorigenesis.
D000256:Adenoviridae / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis*; D004587:Electrophoresis, Agar Gel; D006801:Humans
D000951:Antigens, Neoplasm; D004279:DNA, Viral