Adenovirus E1A gene induction of susceptibility to lysis by natural killer cells and activated macrophages in infected rodent cells.
Rodent cells immortalized by the E1A gene of nononcogenic adenoviruses are susceptible to lysis by natural killer (NK) cells and activated macrophages. This cytolysis-susceptible phenotype may contribute to the rejection of adenovirus-transformed cells by immunocompetent animals. Such increased cytolytic susceptibility has also been observed with infected rodent cells. This infection model provided a means to study the role of E1A gene products in induction of cytolytic susceptibility without cell selection during transformation. Deletion mutations outside of the E1A gene had no effect on adenovirus type 2 (Ad2) or Ad5 induction of cytolytic susceptibility in infected hamster cells, while E1A-minus mutant viruses could not induce this phenotype. E1A mutant viruses that induced expression of either E1A 12S or 13S mRNA in infected cells were competent to induce cytolytic susceptibility. Furthermore, there was a correlation between the accumulation of E1A gene products in Ad5-infected cells and the level of susceptibility of such target cells to lysis by NK cells. The results of coinfection studies indicated that the E1A gene products of highly oncogenic Ad12 could not complement the lack of induction of cytolytic susceptibility by E1A-minus Ad5 virus in infected cells and also could not block induction of this infected-cell phenotype by Ad5. These data suggest that expression of the E1A gene of nononcogenic adenoviruses may cause the elimination of infected cells by the immunologically nonspecific host inflammatory cell response prior to cellular transformation. The lack of induction of this cytolysis-susceptible phenotype by Ad12 E1A may result in an increased persistence of Ad12-infected cells in vivo and may lead to an increased Ad12-transformed cell burden for the host.
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic; D005260:Female; D005796:Genes; D005814:Genes, Viral; D007694:Killer Cells, Natural / Q000276:immunology*; D008242:Lysogeny; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008647:Mesocricetus; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains
D017456:Adenovirus Early Proteins; D009856:Oncogene Proteins, Viral