Isolation of type 5 adenovirus mutants with a cold-sensitive host range phenotype: Genetic evidence of an adenovirus transformation maintenance function

Role of the adenovirus early region 1B tumor antigens in transformation and lytic infection

“…A severe host-range phenotype was also reported for other Ad5 Elb mutants such as hr6 and h?CI (Harrison et aL, 1977;Ho et aL, 1982) which are also defective in expression of the 58-kDa protein (Lassam et aL, 1979). A less drastic growth defect on HeLa cells (loo-fold reduced) was recently reported for the Ad5 58-kDa mutant dl.338 .…”

“…The latter authors showed that the efficiency of transformation decreased with decreasing size of the residual 58-kDa truncated product. The observation that Ad5 group II hr mutants, which are defective in the synthesis of the 58kD protein, were unable to transform BRK cells (Graham et al, 1978;Ho et al, 1982;Mak and Mak, 1983) may possibly be explained by the fact that these mutants express only very short truncated fragments of the 58-kDa protein. The finding that DNA extracted from the hr II mutant virions did have transforming activity on BRK cells (Rowe and Graham, 1983) indicates that virus-mediated transformation is more dependent on the size of the 58-kDa truncated product than DNA-mediated transformation.…”

“…Since cells transformed by this fragment do not express the 58-kDa Elb protein, these results suggested that this protein is not required for complete morphological transformation (Schrier et al, 1979). In contrast, viruses that fail to express the 58-kDa Elb protein are unable to transform a variety of primary cells (Graham et ab, 1978;Ho et al, 1982), although DNA extracted from these mutant viruses was capable of transforming rodent cells. This suggested that the 58-kDa protein is required for virus-mediated transformation but not for DNA-mediated transformation (Rowe and Graham, 1983).…”

Viruses – seeking and destroying the tumor program

“…In many ways, the cellular response to heat shock resembles the late stages of adenovirus infection; the translation of cellular mRNAs is inhibited, while heat shock mRNAs are preferentially translated. dl1520/ONYX-015 is known to be a 'cold sensitive' virus, exhibiting defective late protein translation and replication in tumor cells incubated at 321C (Ho et al, 1982;Leppard and Shenk, 1989;Harada and Berk, 1999). Recently, we examined if this might instead be a 'heat-dependency' phenotype, and if heat shock could rescue ONYX-015 late viral protein expression in resistant tumor cell lines.…”

Deletion mutants of region E1 a of AD12 E1 plasmids: Effect on oncogenic transformation

“…Not all mutants in the 13 S messenger are transformation-deficient, however. Ad5 hr 1, which carries a deletion at a similar position as hr 440, can transform baby rat kidney cells (Graham et al, 1978) and, at a slightly elevated temperature, also other primary rat cells (Ho et aL, 1982).…”