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Updated: Jun 17, 2026
Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
Published on: June 25, 2012
Contamination with E1A-positive wild-type adenovirus accounts for species-specific stimulation of islet cell
Jeremy A Lavine1, Philipp W Raess, Dawn B Davis
1Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Abstract:
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.
Insights
Adenovirus-mediated preprocholecystokinin (CCK) did not cause islet cell proliferation in mice or humans due to E1A contamination. However, CCK expression did stimulate proliferation in rat islets, highlighting the need for careful vector purification.
Area of Science:
- Endocrinology
- Molecular Biology
- Virology
Background:
- Previous studies suggested adenovirus-mediated preprocholecystokinin (CCK) expression stimulated human and mouse islet cell proliferation.
- Concerns arose regarding potential contamination of the CCK adenovirus vector with wild-type adenovirus expressing E1A.
Discussion:
- This study conclusively demonstrates that the previously reported proliferative effects in human and mouse islets were due to E1A contamination, not CCK.
- CCK expression was confirmed to induce proliferation specifically in rat islets, indicating species-specific effects.
- The methodology for detecting wild-type adenovirus contamination and purifying viral stocks is detailed to aid other researchers.
Key Insights:
- Adenovirus E1A contamination, not CCK, was responsible for observed islet cell proliferation in human and mouse models.
- CCK expression exhibits proliferative effects in rat islets, suggesting species-specific biological activity.
- Rigorous detection and purification of viral vectors are crucial for accurate research outcomes, especially in cell replication studies.
Outlook:
- Further investigation into the precise mechanisms of CCK-induced proliferation in rat islets.
- Development of improved purification techniques for adenovirus vectors to prevent contamination.
- Re-evaluation of previous studies using similar adenovirus vectors for potential contamination artifacts.
