Deletion of the gene encoding the adenovirus 5 early region 1b 21,000-molecular-weight polypeptide leads to degradation of viral and host cell DNA

Abstract

The adenovirus 5 mutant H5dl337 lacks 146 base pairs within early region 1B. The deletion removes a portion of the region encoding the ElB 21,000-molecular-weight (21K) polypeptide, but does not disturb the ElB-55K/17K coding region. The virus is slightly defective for growth in cultured HeLa cells, in which its final yield is reduced ca. 10-fold compared with wild-type virus. The mutant displays a striking phenotype in HeLa cells. The onset of cytopathic effect is dramatically accelerated, and both host cell and viral DNAs are extensively degraded late after infection. This defect has been described previously for a variety of adenovirus mutants and has been termed a cytocidal (cyt) phenotype. H5dl337 serves to map this defect to the loss of E1B-21K polypeptide function. In addition to its defect in the productive growth cycle, H5dl337 is unable to transform rat cells at normal efficiency.

Acceleration of virus‐induced apoptosis by tumor necrosis factor

“…Previous studies on the effects of apoptosis on the in vitro replication and the in vivo infectivity of a baculovirus revealed that a host apoptotic response provides protection against virus infection at the organismal level [8], suggesting that the virus‐induced apoptosis can have some role in a host defense mechanism [9, 10]. In agreement with this hypothesis, apoptotic cell death concomitantly brings an abortion of the progeny virus production in some cases of animal virus infections in vitro [11–13], although there are a number of exceptions, especially in the infection with RNA viruses [14–17].…”

Induction of apoptosis limits cytomegalovirus cross-species infection

“…The present study shows that certain β‐herpesviruses—large DNA viruses that replicate their genomes in the nucleus—induce apoptosis in cells of a foreign species, even though they can inhibit premature apoptosis in cells of their own species. A number of other viruses also depend on inhibition of apoptosis for normal replication, and consequently they encode potent cell death suppressors: Adenoviruses and γ‐herpesviruses are two prominent examples (Pilder et al , 1984; White et al , 1984; Altmann and Hammerschmidt, 2005). It is possible that the species restriction of these viruses also depends (in part) on their ability to inhibit cell death in cells of a foreign species, even if in the end more than one mechanism should turn out to be involved, as it appears to be the case for human CMV.…”

Apoptosis and the cell cycle

“…A similar interpretation may apply to induction of apoptosis in quiescent cells by adenovirus E 1A. Adenovirus E 1A induces apoptosis when expressed in the absence of E1B 19K, a second adenovirus protein [Pilder et al, 1984;Rao et al, 1992;Subramanian et al, 1984;White et al, 1984a,b, 19921. Infection of normal rat ludney cells with an adenovirus producing only the E 1A protein and lacking the E1B region caused apoptosis only when the cells were growth arrested, either by growth to confluence or by serum starvation [Mymryk et al, 19941.…”