The Mode of Death of Pig Kidney Cells Infected with Cowpox Virus Is Governed by the Expression of thecrmAGene

AbstractPig kidney cells (LLC-PK1) were infected with one of three viruses: wild-type cowpox virus (Brighton red strain) expressing thecrmAgene; recombinant cowpox virus A602, lacking thecrmAgene; or cowpox virus A604, a revertant of virus A602, expressing thecrmAgene. The wild-type virus and virus A604 produced identical cytopathic effects consistent with death by necrosis. In these cells, the structural features of the plasma membrane, the nuclear membrane, and the chromatin were maintained until lysis of the cells. In contrast, cowpox virus A602 produced cytopathic effects consistent with death by apoptosis. These effects included loss of microvilli on the cell surface, margination and condensation of the chromatin, progressive convolution of the nuclear membrane, release of dense chromatin masses on disintegration of the nucleus, fragmentation of the DNA, and the generation of apoptotic bodies. These results suggest that thecrmAgene is necessary to inhibit processes of apoptosis induced in LLC-PK1cells by infection with cowpox virus. Thus in cells of certain types, thecrmAgene can act with other viral genes to control the mode of death of the virus-infected cell. This capability may be advantageous to virus replicationin vivo,potentially facilitating both virus trafficking and interference with antiviral immune defenses