Adenovirus Serotype 5 Variants Defective in Early Genes: Selective Replication in p53-Deficient Human Tumor Cells

Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293...

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Bibliographic Details
Published in:Molecular biology (New York) 2003-09, Vol.37 (5), p.739-745
Main Authors: Kachko, A V, Svyatchenko, V A, Ternovoi, V A, Kiselev, N N, Sorokin, A V, Kiselev, S L, Georgiev, G P, Netesov, S V
Format: Article
Language:English
Subjects:
Adenovirus
Adenoviruses
Animal models
Carcinoma
Cell culture
Human adenovirus
Infection
p53 protein
Permissive cells
Replication
Rodents
Serotypes
Site-directed mutagenesis
Tumor cells
Tumors
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Summary:Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293 line. Mutant Adel2 with deletion from E1B55K infected the 293 line cells and p53-deficient human tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5, whereas its replication in normal p53-positive cells was substantially limited. Thus, Adel2 proved to be capable of selective infection and lysis of p53-deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is thus a promising model for designing therapeutic agents against p53-deficient human tumors.[PUBLICATION ABSTRACT]
ISSN:0026-8933
1608-3245
DOI:10.1023/A:1026093112245