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Science 28 February 1997:
Vol. 275. no. 5304, pp. 1320 - 1323
DOI: 10.1126/science.275.5304.1320
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Reports

Isolation of a Common Receptor for Coxsackie B Viruses and Adenoviruses 2 and 5 

Jeffrey M. Bergelson, * Jennifer A. Cunningham, Gustavo Droguett, Evelyn A. Kurt-Jones, Anita Krithivas, Jeong S. Hong, Marshall S. Horwitz, Richard L. Crowell, Robert W. Finberg

A complementary DNA clone has been isolated that encodes a coxsackievirus and adenovirus receptor (CAR). When transfected with CAR complementary DNA, nonpermissive hamster cells became susceptible to coxsackie B virus attachment and infection. Furthermore, consistent with previous studies demonstrating that adenovirus infection depends on attachment of a viral fiber to the target cell, CAR-transfected hamster cells bound adenovirus in a fiber-dependent fashion and showed a 100-fold increase in susceptibility to virus-mediated gene transfer. Identification of CAR as a receptor for these two unrelated and structurally distinct viral pathogens is important for understanding viral pathogenesis and has implications for therapeutic gene delivery with adenovirus vectors.

J. M. Bergelson, J. A. Cunningham, E. A. Kurt-Jones, A. Krithivas, R. W. Finberg, Division of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
G. Droguett and M. S. Horwitz, Departments of Microbiology-Immunology, Cell Biology, and Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J. S. Hong, Department of Cell Biology and Anatomy, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
R. L. Crowell, Department of Microbiology and Immunology, Medical College of Pennsylvania and Hahnemann University, Philadelphia, PA 19102, USA.
*   To whom correspondence should be addressed. E-mail: jeff_bergelson{at}macmailgw.dfci.harvard.edu

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Adenovirus Fiber Shaft Contains a Trimerization Element That Supports Peptide Fusion for Targeted Gene Delivery.
J. Li, S. Lad, G. Yang, Y. Luo, M. Iacobelli-Martinez, F. J. Primus, R. A. Reisfeld, and E. Li (2006)
J. Virol. 80, 12324-12331
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Novel Fiber-Dependent Entry Mechanism for Adenovirus Serotype 5 in Lacrimal Acini.
J. Xie, L. Chiang, J. Contreras, K. Wu, J. A. Garner, L. Medina-Kauwe, and S. F. Hamm-Alvarez (2006)
J. Virol. 80, 11833-11851
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Simultaneous Dystrophin and Dysferlin Deficiencies Associated with High-Level Expression of the Coxsackie and Adenovirus Receptor in Transgenic Mice.
C. A. Shaw, N. Larochelle, R. W.R. Dudley, H. Lochmuller, G. Danialou, B. J. Petrof, G. Karpati, P. C. Holland, and J. Nalbantoglu (2006)
Am. J. Pathol. 169, 2148-2160
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Interaction of Adenovirus Type 5 Fiber with the Coxsackievirus and Adenovirus Receptor Activates Inflammatory Response in Human Respiratory Cells.
A. Tamanini, E. Nicolis, A. Bonizzato, V. Bezzerri, P. Melotti, B. M. Assael, and G. Cabrini (2006)
J. Virol. 80, 11241-11254
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Structural and Mutational Analysis of Human Ad37 and Canine Adenovirus 2 Fiber Heads in Complex with the D1 Domain of Coxsackie and Adenovirus Receptor.
E. Seiradake, H. Lortat-Jacob, O. Billet, E. J. Kremer, and S. Cusack (2006)
J. Biol. Chem. 281, 33704-33716
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Fiber and Penton Base Capsid Modifications Yield Diminished Adenovirus Type 5 Transduction and Proinflammatory Gene Expression with Retention of Antigen-Specific Humoral Immunity.
J. W. Schoggins and E. Falck-Pedersen (2006)
J. Virol. 80, 10634-10644
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Low-Dose Etoposide Enhances Telomerase-Dependent Adenovirus-Mediated Cytosine Deaminase Gene Therapy through Augmentation of Adenoviral Infection and Transgene Expression in a Syngeneic Bladder Tumor Model..
G.-S. Shieh, A.-L. Shiau, Y.-T. Yo, P.-R. Lin, C.-C. Chang, T.-S. Tzai, and C.-L. Wu (2006)
Cancer Res. 66, 9957-9966
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Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes.
A. L. Parker, S. N. Waddington, C. G. Nicol, D. M. Shayakhmetov, S. M. Buckley, L. Denby, G. Kemball-Cook, S. Ni, A. Lieber, J. H. McVey, et al. (2006)
Blood 108, 2554-2561
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Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: manufacture on PER.C6 cells, tropism and immunogenicity..
A. A. C. Lemckert, J. Grimbergen, S. Smits, E. Hartkoorn, L. Holterman, B. Berkhout, D. H. Barouch, R. Vogels, P. Quax, J. Goudsmit, et al. (2006)
J. Gen. Virol. 87, 2891-2899
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Role of the putative heparan sulfate glycosaminoglycan-binding site of the adenovirus type 5 fiber shaft on liver detargeting and knob-mediated retargeting.
N. Bayo-Puxan, M. Cascallo, A. Gros, M. Huch, C. Fillat, and R. Alemany (2006)
J. Gen. Virol. 87, 2487-2495
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Analysis of the interaction between RGD-expressing adenovirus type 5 fiber knob domains and {alpha}vbeta3 integrin reveals distinct binding profiles and intracellular trafficking.
R. Lord, M. Parsons, I. Kirby, A. Beavil, J. Hunt, B. Sutton, and G. Santis (2006)
J. Gen. Virol. 87, 2497-2505
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Transposon-assisted cloning and traceless mutagenesis of adenoviruses: development of a novel vector based on species d..
Z. Ruzsics, M. Wagner, A. Osterlehner, J. Cook, U. Koszinowski, and H.-G. Burgert (2006)
J. Virol. 80, 8100-8113
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Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules.
J. C. Warren, A. Rutkowski, and L. Cassimeris (2006)
Mol. Biol. Cell 17, 3557-3568
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N- and 6-O-Sulfated Heparan Sulfates Mediate Internalization of Coxsackievirus B3 Variant PD into CHO-K1 Cells..
A. E. Zautner, B. Jahn, E. Hammerschmidt, P. Wutzler, and M. Schmidtke (2006)
J. Virol. 80, 6629-6636
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Carcinoembryonic Antigen-Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors..
T. Tanaka, J. Huang, S. Hirai, M. Kuroki, M. Kuroki, N. Watanabe, K. Tomihara, K. Kato, and H. Hamada (2006)
Clin. Cancer Res. 12, 3803-3813
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Adenoviral-encoded antigens are presented efficiently by a subset of dendritic cells expressing high levels of {alpha}v{beta}3 integrins.
A. Harui, M. D. Roth, D. Vira, M. Sanghvi, H. Mizuguchi, and S. K. Basak (2006)
J. Leukoc. Biol. 79, 1271-1278
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Autophagic cell death of malignant glioma cells induced by a conditionally replicating adenovirus..
H. Ito, H. Aoki, F. Kuhnel, Y. Kondo, S. Kubicka, T. Wirth, E. Iwado, A. Iwamaru, K. Fujiwara, K. R. Hess, et al. (2006)
J Natl Cancer Inst 98, 625-636
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Junctional Adhesion Molecule 1 Is a Functional Receptor for Feline Calicivirus.
A. Makino, M. Shimojima, T. Miyazawa, K. Kato, Y. Tohya, and H. Akashi (2006)
J. Virol. 80, 4482-4490
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Comparison of two gene transfer models for the attenuation of myocardial ischemia-reperfusion injury following preservation for cardiac transplantation..
H. Abunasra, R. T. Smolenski, J. Yap, J. Jayakumar, M. Sheppard, and M. H. Yacoub (2006)
Eur. J. Cardiothorac. Surg. 29, 772-778
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