المؤلفون: Karil Abrahamsen, D Brough, H L Kong, A Lizonova, Andrea Mastrangeli, Erik Falck-Pedersen, Ronald G. Crystal

المصدر: Journal of Virology. 71:8946-8951

مصطلحات موضوعية: Gene Expression Regulation, Viral, viruses, Transgene, Genetic Vectors, Immunology, Biology, Virus Replication, Microbiology, Virus, Defective virus, Chloramphenicol acetyltransferase, Mice, Plasmid, Transduction, Genetic, Virology, Animals, Humans, Vector (molecular biology), Cells, Cultured, Adenovirus genome, Adenoviruses, Human, Gene Transfer Techniques, Defective Viruses, Molecular biology, Viral replication, Insect Science, Adenovirus E1A Proteins, Research Article

الوصف: A strategy for constructing replication-defective adenovirus vectors from non-subgroup C viruses has been successfully demonstrated with adenovirus type 7 strain a (Ad7a) as the prototype. An E1A-deleted Ad7a reporter virus expressing the chloramphenicol acetyltransferase (CAT) gene from the cytomegalovirus promoter enhancer was constructed with DNA fragments isolated from Ad7a, an Ad7a recombination reporter plasmid, and the 293 cell line. The Ad7a-CAT virus particle transduces A549 cells as efficiently as Ad5-based vectors. Intravenous infections in a murine model indicate that the Ad7a-CAT virus infects a variety of tissues, with maximal levels of CAT gene expression found in the liver. The duration of Ad7a-CAT transgene expression in the liver was maximally maintained 2 weeks postinfection, with a decline to baseline activity by the week 4 postinfection. Ad7a-CAT represents the first example of a non-subgroup C E1A- adenovirus gene transfer vector.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c7be7bad30c94b03c10fe8431b60e38Test
https://doi.org/10.1128/jvi.71.11.8946-8951.1997Test

المؤلفون: Jose M. Trevejo, Erik Falck-Pedersen, Ronald G. Crystal, Chau Ching Liu, Xin Song, Lloyd J. Old, Keith B. Elkon, Karil Abrahamsen, Michael W. Marino, Jun Liang Zhou, Jason G. D. Gall

مصطلحات موضوعية: Genetic Vectors, Inflammation, medicine.disease_cause, Virus, Adenoviridae, Cell Line, Mice, Immune system, Immunity, medicine, Animals, Multidisciplinary, biology, Effector, Tumor Necrosis Factor-alpha, Gene Transfer Techniques, Biological Sciences, Virology, Mice, Inbred C57BL, Perforin, Immunology, biology.protein, Tumor necrosis factor alpha, medicine.symptom

الوصف: Adenovirus (Ad) gene transfer vectors are rapidly cleared from infected hepatocytes in mice. To determine which effector mechanisms are responsible for elimination of the Ad vectors, we infected mice that were genetically compromised in immune effector pathways [perforin, Fas, or tumor necrosis factor α (TNF-α)] with the Ad vector, Ad5-chloramphenicol acetyl transferase (CAT). Mice were sacrificed at 7–60 days postinfection, and the levels of CAT expression in the liver determined by a quantitative enzymatic assay. When the livers of infected mice were harvested 28 days postinfection, the levels of CAT expression revealed that the effectors most important for the elimination of the Ad vector were TNF-α > Fas > perforin. TNF-α did not have a curative effect on infected hepatocytes, as the administration of TNF-α to infected severe combined immunodeficient mice or to infected culturesin vitrohad no specific effect on virus persistence. However, TNF-α-deficient mice demonstrated a striking reduction in the leukocytic infiltration early on in the infection, suggesting that TNF-α deficiency resulted in impaired recruitment of inflammatory cells to the site of inflammation. In addition, the TNF-deficient mice had a significantly reduced humoral immune response to virus infection. These results demonstrate a dominant role of TNF-α in elimination of Ad gene transfer vectors. This result is particularly important because viral proteins that disable TNF-α function have been removed from most Ad vectors, rendering them highly susceptible to TNF-α-mediated elimination.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fda16e9d42eda1d7d0776e63d70b57edTest
https://europepmc.org/articles/PMC23274Test/