We have previously reported that adenovirus-mediated expression of preprocholecystokin (CCK) stimulates human and mouse islet cell proliferation. In follow-up studies, we became concerned that the CCK adenovirus might have been contaminated with a wild-type E1A-containing adenovirus. Here we show conclusively that the proliferative effects reported in the original paper in mouse and human islets were not due to CCK expression but rather to a contaminating E1A-expressing wild-type adenovirus. We also show, however, that CCK expression does have a proliferative effect in rat islets. We hope that our report of the steps taken to detect the wild-type virus contamination, and purification of the contributing viral stocks, will be helpful to other investigators, and that our experience will serve as a cautionary tale for use of adenovirus vectors, especially for studies on cellular replication.
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http://dx.doi.org/10.1210/me.2009-0384 | DOI Listing |
J Biol Chem
January 2025
Division of Experimental Animal, Hidaka Branch, Biomedical Research Center, Saitama Medical University, Saitama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. Electronic address:
Recent success with the use of glucagon-like peptide-1 (GLP-1) receptor analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors for the treatment of patients with diabetes has highlighted the role of the intestine as an endocrine organ. Gut-derived hormones, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, have important roles in the control of energy metabolism and food intake, and are associated with the metabolic syndrome. In this study, we isolated and identified a new intestine-derived hormone, betagenin, and showed that it stimulates insulin secretion and β-cell proliferation and suppresses β-cell apoptosis.
View Article and Find Full Text PDFVaccines (Basel)
December 2024
Laboratory of Immunochemistry, National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, 115522 Moscow, Russia.
Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of these antibodies. The avidity of serum antibodies is associated with a vaccine showing high effectiveness and reflects the process of affinity maturation.
View Article and Find Full Text PDFJ Virol
December 2024
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Protein kinase R (PKR) is an interferon-induced antiviral protein activated by autophosphorylation in response to double strand DNA (dsRNA) and other stimuli. Activated PKR causes translation inhibition and apoptosis, and it contributes to proinflammatory responses, cell growth, and differentiation. Mouse adenovirus type 1 (MAV-1) counteracts PKR by causing its degradation via a viral protein, early region 4 open reading frame 6 (E4orf6).
View Article and Find Full Text PDFTwo live attenuated vaccines (LAVs), LMA and LMP, were evaluated alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV) for their efficacy and immune responses in wild type (WT) and interferon gamma (IFNγ) knockout (KO) mice in a C57BL/6 background. While LMA and LMP are triple deletion mutants of CO92 strain, Ad5-YFV incorporates three protective plague immunogens. An impressive 80-100% protection was observed in all vaccinated animals against highly lethal intranasal challenge doses of parental CO92.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2024
Genomic Medicine Unit CMC, Global CMC Development, Sanofi R&D, 225 2nd Avenue, Waltham, MA 02451, USA.
Efficient manufacturing of recombinant adenovirus-associated virus (AAV) vectors is critical to the successful development of genomic medicines. We attempted to optimize AAV vector production in a producer cell line platform. In this system, helper functions required for AAV replication and production are provided via infection with a replication-competent wild-type Adenovirus.
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