1887

Abstract

SUMMARY

An adenovirus (Ad) interserotypic recombinant (H2141) between temperature-sensitive mutant H2111 of Ad2 and deletion mutant H5313 of Ad5 was isolated and characterized. It was phenotypically , , and formed large plaques (or cytocidal: ). It contained the right 89% of Ad5 DNA and the leftmost 11% of Ad2 DNA. Genetic recombination data suggested the cytocidal mutation lay in the transforming region E1B, confirming sequence analysis. The cytocidal effect resulted in part from the breakdown of cellular DNA. Host cell and virus DNA breakdown induced by H2141 appeared cell-dependent: it occurred in HeLa, KB or BHK-21 cells, but not in CV1 or 293 cells. In human cells the effect was recessive and adenovirus DNA degradation was prevented by co-infection with adenovirus wild-type (H2WT), other adenovirus serotypes or simian virus 40 (SV40). In simian cells, H2141 did not inhibit SV40 DNA replication, unlike H2WT. The amount of H2141 DNA integrated in human cell DNA at early stages of the lytic cycle was found to be significantly lower than for H2WT. Novobiocin inhibited viral DNA breakdown in human cells. Cellular DNA extracted from H2141-infected cells exhibited a repeat band pattern in gel electrophoresis reminiscent of the nuclease digestion pattern of chromatin, with monosome-size fragments as the digestion limit. The H2141-induced nucleolytic effect would therefore occur in the linker regions of cell DNA and might result from the observed stimulation (by a factor of greater than 100) of an acidic (optimum pH 4.0) endonuclease activity. The nucleolytic effect also appeared to be recessive and absent in mixed samples containing extracts from H2141-infected cells plus extracts from H2WT- or mock-infected cells. The virus gene product responsible for the enhancement of the acidic endonuclease was found to function stoichiometrically and not catalytically. The cytocidal and nucleolytic effects of the viral E1B region 19K protein may be mediated by a cellular inhibitor of acidic endonuclease.

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1985-09-01
2021-10-28
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