An adenovirus type 5 gene function required for initiation of viral DNA replication

Vliet, Peter C. van der; Sussenbach, J.S.

doi:10.1016/0042-6822(75)90443-2

Cited by 146 publications

(66 citation statements)

References 29 publications

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“…Neutral sucrose gradients in the presence of 0.5% NaDodSO4 were used for these analyses. Fig (22,31). Van der Vliet et al observed that the apparent rate of elongation of Ad DNA was normal after shift to nonpermissive temperature even though the amount of synthesis was reduced by greater than 80%.…”

Section: Resultsmentioning

confidence: 99%

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Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Horwitz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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A soluble adenovirus DNA replication system has been prepared in extracts of HeLa cells infected with the temrperature-sensitive mutant HMts125. These nuclear extracts synthesize full-sized viral DNA at 300 but are temperature sensitive in this function at 380. A 72,000-dalton DNA-binding protein purified from cells infected with wild-type virus complements the temperature-sensitive defect and restores viral DNA replication to 74% of normal values. We have recently described the preparation of a nuclear extract from adenovirus (Ad)infected cells that catalyzed the synthesis of viral DNA in a manner analogous to that used in whole cells (1). These extracts, which were free of chromosomal DNA, contained replicating Ad DNA and synthesized full-size viral DNA products. Similar approaches developed in prokaryotes and their infecting bacteriophages have allowed the analysis of various gene products required for DNA initiation and elongation (2)(3)(4)(5). The general approach has been to prepare extracts from bacterial cell mutants that are temperature sensitive (ts) in DNA synthesis and to use these extracts as a receptor to isolate biochemically complementing activity from wild-type

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Section: Resultsmentioning

confidence: 99%

“…The ts DBP made at the permissive temperature has a different temperature coefficient of binding to columns of single-stranded DNA-cellulose from that of wt DBP (21). In whole cells infected with H5ts125, the defect in Ad DNA synthesis has been reported to be a failure of initiation (22).…”

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confidence: 99%

Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Horwitz¹

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…E1A is both a positive and a negative transcription regulator of specific viral and cellular genes (13)(14)(15)(16). E1A induces transcription of genes involved in adenovirus DNA replication (17)(18)(19). The E1B 55-kDa protein in concert with E4 ORF6 proteins is important for viral RNA transport (20).…”

Section: Introductionmentioning

confidence: 99%

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Ghosh

Duigou

2005

Cancer Research

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E1 region replacement adenoviruses are replication defective and are propagated in cells providing adenovirus E1A and E1B proteins. Although they are being developed for antitumor therapies, the proliferative behaviors of these viruses in normal brain tissues or in brain tumors are unknown. To address this, freshly cultured cells from normal human brain and common brain tumors (astrocytomas and meningiomas) were infected using wild-type species C adenoviruses and adenoviruses missing E1A (H5dl312) or E1A plus E1B (H5dl434). Viral DNA replication, late viral protein expression, and production of infectious progeny were characterized. Wild-type adenoviruses grew efficiently in normal brain and brain tumor cells. In comparison, E1-deleted adenovirus DNA replication was delayed and lower in cells derived from normal brain tissues, meningiomas, and low-grade astrocytomas. However, in contrast, E1-deleted adenovirus DNA replication did not occur or was extremely low in cells derived from malignancy grade III and IV astrocytic tumors. Because wild-type adenoviruses infected and replicated in all cells, the malignancy grade-based differential E1-deleted adenovirus DNA replication was not explained by differential virus uptake. Infectious H5dl312 and H5dl434 production correlated with viral DNA replication. Compared with a 5-day average for wild-type infections, advanced cytopathology was noted f4 weeks after H5dl312 or H5dl434 infection of meningioma, astrocytoma, and normal brain cells. Cytopathology was not observed after H5dl312 or H5dl434 infection of glioblastoma, anaplastic astrocytoma, and gliosarcoma cells. Because of this tumor grade-based differential growth, the E1-deleted adenoviruses may represent novel tools for studies of brain tumor malignancy. (Cancer Res 2005; 65(19): 8936-43)

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“…Several mutants with temperature sensitive (tsj alterations in the DBP have been indispensable in defining several of the functions of this protein. The ts alterations at the nonpermissive temperature diminish the single-strand, DNA-binding activity of the protein in vitro (52) and inhibit DNA replication in vivo (13,47,53) and in vitro (20). Normal turn-off of viral early genes during the late phase of the lytic cycle is also disrupted at the nonpermissive temperature in cells infected with the ts mutant (6,9,10,37,38).…”

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Introduction, stable integration, and controlled expression of a chimeric adenovirus gene whose product is toxic to the recipient human cell.

Klessig¹,

Brough²,

Cleghon³

1984

Mol. Cell. Biol.

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The DNA-bindihg protein (DBP) encoded by human adenoviruses is a multifunctional polypeptide which plays a central iole in regulating the expression of the viral genes. To gain a better understanding of the relationships between the various functions provided by IBP, an extensive collection of DBP mutants is essential. To this end we have constructed several permissive human cell lines which contain and express the DBP gene at high levels to allow propagation of otherwise lethal, nonrecoverable mutants of DBP. Because DB3P is totic to human cells, cell lines were constructed by using a vector in which the DBP gene is under the control of the dexamethasone-inducible promoter of the mouse mammary tumor virus. The low basal levels of DBP synthesis in the absence of dexamethasone allows isolation and propagation of these cells. Addition of dexamethasone enhances DBP production 50-to 200-fold, and within 8 h its synthesis fromb the single integrated copy of the chimeric gene is 5 to 15% of that observed during peak DBP synthesis in infected human cells in which hundreds of copies of the DBP gene serve as templates. At the nonpermissive temperature, adenovirus mutants with ts lesions in the DBP gene replicate their DNAs, express their late genes, and form infectious viral particles in these DBP+ cell lines but not in the parental HeLa cells.A number of multifunctional proteins in euearyotes have been defined by,a combination of genetic and biochemical studies. One of the best characterized of these is the simian virus 40 (SV40) large T antigen, which exhibits separate functional domains as discerned by mapping of sets of mutations which alter one but not another of the various protein functions.The human adenovirus 72-kilodalton DNA-binding protein (DBP) also plays several independent roles during the infectious cycle of this virus. Several mutants with temperature sensitive (tsj alterations in the DBP have been indispensable in defining several of the functions of this protein. The ts alterations at the nonpermissive temperature diminish the single-strand, DNA-binding activity of the protein in vitro (52) and inhibit DNA replication in vivo (13, 47, 53) and in vitro (20). Normal turn-off of viral early genes during the late phase of the lytic cycle is also disrupted at the nonpermissive temperature in cells infected with the ts mutant (6,9,10,37,38). The DBP directly affects early gene turn-off as well as DNA replication, since inhibition of viral DNA synthesis with either drugs or ts lesions in other viral early genes does not affect early gene expression (9, 10). In addition, at the nonpermissive temperatui*, the ts mutants transform rat cells in culture with an enhanced frequency compared with wild-type (wt) virus (16,54).A second class of mutants which greatly enhance the ability of this human virus to grow in monkey cells defines yet a second set of functions of DBP (1,26,29). In monkey cells infected with wt human adenovirus, the viral early genes are properly expressed (3), and viral DNA replication occurs no...

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An adenovirus type 5 gene function required for initiation of viral DNA replication

Cited by 146 publications

References 29 publications

Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Temperature-sensitive replication of H5ts125 adenovirus DNA in vitro.

Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy

Introduction, stable integration, and controlled expression of a chimeric adenovirus gene whose product is toxic to the recipient human cell.

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