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Journal of Virology, June 2004, p. 6431-6438, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6431-6438.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Biodistribution of Radioiodinated Adenovirus Fiber Protein Knob Domain after Intravenous Injection in Mice

Vibhudutta Awasthi,1,{dagger} George Meinken,1 Karen Springer,2 Suresh C. Srivastava,1 and Paul Freimuth2*

Biology Department,2 Medical Department, Brookhaven National Laboratory, Upton, New York 119731

Received 18 December 2003/ Accepted 11 February 2004

The knob domains from the fiber proteins of adenovirus serotypes 2 and 12 were labeled with radioiodine and then injected into the bloodstreams of mice. Knob proteins with functional binding sites for the coxsackie and adenovirus receptor (CAR) were cleared rapidly from the circulation, with radioactivity appearing predominantly in the stomach, while knob mutants unable to bind to CAR remained in the blood circulation for a prolonged period. The clearance of radiolabeled wild-type knob from the blood was slowed by coinjecting an excess of unlabeled wild-type knob protein. An earlier study showed that 99mTc-labeled knob protein with intact CAR-binding activity also cleared rapidly from the blood circulation of mice, with radioactivity accumulating predominantly in the liver (K. R. Zinn et al., Gene Ther. 5:798-808, 1998). Together these results suggest that rapid clearance of knob protein from the blood results from specific binding to CAR in the liver and that the bound knob then enters a degradative pathway. The elevated levels of radioiodine in the stomach observed in our experiments are consistent with deiodination of labeled knob by dehalogenases in hepatocyte microsomes and uptake of the resultant free radioiodine by Na/I symporters in the gastric mucosa. Although CAR has been shown to localize in tight junctions of polarized epithelial cells, where it functions in intercellular adhesion, the results of our study suggest that a subset of CAR molecules in the liver is highly accessible to ligands in the blood and able to rapidly deliver bound ligand to an intracellular degradative compartment.

* Corresponding author. Mailing address: Biology Department, Brookhaven National Laboratory, Upton, NY 11973. Phone: (631) 344-3350. Fax: (631) 344-3407. E-mail: freimuth{at}bnl.gov.

{dagger} Present address: Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900.

Journal of Virology, June 2004, p. 6431-6438, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6431-6438.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xie, J., Chiang, L., Contreras, J., Wu, K., Garner, J. A., Medina-Kauwe, L., Hamm-Alvarez, S. F. (2006). Novel Fiber-Dependent Entry Mechanism for Adenovirus Serotype 5 in Lacrimal Acini. J. Virol. 80: 11833-11851 [Abstract] [Full Text]  


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