An adenovirus early region 1A protein is required for maximal viral DNA replication in growth-arrested XXXX cells.

@entity35 @entity1 @entity1522 @entity535
Two closely related adenovirus early region 1A proteins are expressed in transformed cells. The smaller of these, which is 243 @entity1522 in length, is required for the transformation of primary @entity35 cells and for the transformation of immortalized @entity35 cells to anchorage-independent growth. This protein is not required for productive infection of exponentially growing HeLa cells but is required for maximal replication in growth (G0)-arrested @entity1 lung fibroblasts ( @entity1 cells). To determine the function of this protein in viral replication in these G0-arrested cells, we compared viral early mRNA, early protein, and late protein synthesis after infection with wild type or a mutant which does not express the protein. No differences were found. However, viral DNA synthesis by the mutant was delayed and decreased to 20 to 30% that of wild type in these cells. Viral DNA synthesis was much less defective in growing @entity1 cells, and in the transformed @entity1 HeLa cell line it occurred at wild-type levels. Furthermore, the mutant which can express only the 243- @entity535 early region 1A protein induced cellular DNA synthesis in G0-arrested @entity35 cells to the same level as wild-type virus. A mutant which can express only the 289- @entity535 early region 1A protein induced less cellular DNA synthesis in G0-arrested @entity35 cells. We propose that the early region 1A 243- @entity535 protein alters the physiology of arrested permissive cells to allow maximal viral DNA replication. In nonpermissive rodent cells, the 243- @entity535 protein drives G0-arrested cells into S phase. This activity is probably important for the immortalization of primary cells.
