5-Fluorouracil-related enhancement of adenoviral infection is Coxsackievirus-adenovirus receptor independent and associated with morphological changes in lipid membranes.

Abstract

AIM:

To evaluate the mechanism underlying the effects of 5-Fluorouracil (5-FU) on adenoviral infection.

METHODS:

Low and high Coxsackievirus-Adenovirus Receptor (CAR) expressing human colon carcinoma cell lines were treated with 5-FU and two E1-deleted adenoviral constructs, one transferring GFP (Ad/CMV-GFP) the other bax (Ad/CEA-bax). The number of infected cells were monitored by GFP expression. To evaluate the effects of 5-FU in a receptor free system, Ad/GFP were encapsulated in liposomes and treated with 5-FU. Ad/GFP release was estimated with PCR and infection of 293 cells with the supernatant. Electron microscopy of the Ad5-GFP-liposome complex was made to investigate morphological changes of the liposomes after 5-FU.

RESULTS:

Infection rates of all cell lines increased from 50% to 98% with emerging 5-FU concentrations. The enhanced viral uptake was independent of the CAR expression. Additionally, 5-FU treated liposomes released 2-2.5 times more adenoviruses. Furthermore, 5-FU-treated liposomes appeared irregular and porous-like.

CONCLUSION:

Adenoviral uptake is enhanced in the presence of 5-FU irrespective of CAR and is associated with morphological changes in membranes making the combination of both a promising option in gene therapy.

• Authors: Chiara Cabrele, Mandy Vogel, Pompiliu Piso, Markus Rentsch, Josef Schröder, Karl W Jauch, Hans J Schlitt, Alexander Beham
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 12 Issue 32 Pg. 5168-74 (Aug 28 2006) ISSN: 1007-9327 [Print] United States
• PMID: 16937527 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• CLMP protein, human
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Lipids
• Liposomes
• Receptors, Virus
• Green Fluorescent Proteins
• Fluorouracil

Topics

• Adenoviridae Infections (drug therapy)
• Antimetabolites, Antineoplastic (pharmacology)
• Cell Line
• Cell Line, Tumor
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Fluorouracil (pharmacology)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Genetic Vectors (chemistry)
• Green Fluorescent Proteins (chemistry)
• Humans
• Lipids (chemistry)
• Liposomes (chemistry)
• Membranes (chemistry)
• Receptors, Virus (metabolism, physiology)