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J Biol Chem, Vol. 274, Issue 15, 10219-10226, April 9, 1999
From the Departments of Internal Medicine, Howard Hughes Medical
Institute, Physiology and Biophysics, University of Iowa College of
Medicine, Iowa City, Iowa 52242, the Recent identification of two receptors for the
adenovirus fiber protein, coxsackie B and adenovirus type 2 and 5 receptor (CAR), and the major histocompatibility complex (MHC) Class I
Basolateral Localization of Fiber Receptors Limits Adenovirus
Infection from the Apical Surface of Airway Epithelia
, Division of
Immunologic and Infectious Diseases, Children's Hospital of
Philadelphia, Philadelphia, Pennsylvania 19104, and the ¶ Dana
Farber Cancer Institute, Boston, Massachusetts 02115
-2 domain allows the molecular basis of adenoviral infection to be
investigated. Earlier work has shown that human airway epithelia are
resistant to infection by adenovirus. Therefore, we examined the
expression and localization of CAR and MHC Class I in an in vitro model of well differentiated, ciliated human airway
epithelia. We found that airway epithelia express CAR and MHC Class I. However, neither receptor was present in the apical membrane; instead, both were polarized to the basolateral membrane. These findings explain
the relative resistance to adenovirus infection from the apical
surface. In contrast, when the virus was applied to the basolateral
surface, gene transfer was much more efficient because of an
interaction of adenovirus fiber with its receptors. In addition, when
the integrity of the tight junctions was transiently disrupted, apically applied adenovirus gained access to the basolateral surface and enhanced gene transfer. These data suggest that the receptors required for efficient infection are not available on the apical surface, and interventions that allow access to the basolateral space
where fiber receptors are located increase gene transfer efficiency.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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Y. Man, V. J. Hart, C. J. A. Ring, S. Sanjar, and M. R. West Loss of Epithelial Integrity Resulting from E-Cadherin Dysfunction Predisposes Airway Epithelial Cells to Adenoviral Infection Am. J. Respir. Cell Mol. Biol., November 1, 2000; 23(5): 610 - 617. [Abstract] [Full Text]
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G. Wang, C. Deering, M. Macke, J. Shao, R. Burns, D. M. Blau, K. V. Holmes, B. L. Davidson, S. Perlman, and P. B. McCray Jr. Human Coronavirus 229E Infects Polarized Airway Epithelia from the Apical Surface J. Virol., October 1, 2000; 74(19): 9234 - 9239. [Abstract] [Full Text]
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N. Arnberg, A. H. Kidd, K. Edlund, F. Olfat, and G. Wadell Initial Interactions of Subgenus D Adenoviruses with A549 Cellular Receptors: Sialic Acid versus alpha v Integrins J. Virol., August 15, 2000; 74(16): 7691 - 7693. [Abstract] [Full Text]
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I. Dmitriev, E. Kashentseva, B. E. Rogers, V. Krasnykh, and D. T. Curiel Ectodomain of Coxsackievirus and Adenovirus Receptor Genetically Fused to Epidermal Growth Factor Mediates Adenovirus Targeting to Epidermal Growth Factor Receptor-Positive Cells J. Virol., August 1, 2000; 74(15): 6875 - 6884. [Abstract] [Full Text]
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R. J. Pickles, J. A. Fahrner, J. M. Petrella, R. C. Boucher, and J. M. Bergelson Retargeting the Coxsackievirus and Adenovirus Receptor to the Apical Surface of Polarized Epithelial Cells Reveals the Glycocalyx as a Barrier to Adenovirus-Mediated Gene Transfer J. Virol., July 1, 2000; 74(13): 6050 - 6057. [Abstract] [Full Text]
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R. K. Batra, S. M. Dubinett, B. W. Henkle, S. Sharma, and B. K. Gardner Adenoviral Gene Transfer Is Inhibited by Soluble Factors in Malignant Pleural Effusions Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 613 - 619. [Abstract] [Full Text]
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J. Zabner, M. Seiler, R. Walters, R. M. Kotin, W. Fulgeras, B. L. Davidson, and J. A. Chiorini Adeno-Associated Virus Type 5 (AAV5) but Not AAV2 Binds to the Apical Surfaces of Airway Epithelia and Facilitates Gene Transfer J. Virol., April 15, 2000; 74(8): 3852 - 3858. [Abstract] [Full Text]
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I. Kirby, E. Davison, A. J. Beavil, C. P. C. Soh, T. J. Wickham, P. W. Roelvink, I. Kovesdi, B. J. Sutton, and G. Santis Identification of Contact Residues and Definition of the CAR-Binding Site of Adenovirus Type 5 Fiber Protein J. Virol., March 15, 2000; 74(6): 2804 - 2813. [Abstract] [Full Text]
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G. P. Linette, S. Shankara, S. Longerich, S. Yang, R. Doll, C. Nicolette, F. I. Preffer, B. L. Roberts, and F. G. Haluska In Vitro Priming with Adenovirus/gp100 Antigen-Transduced Dendritic Cells Reveals the Epitope Specificity of HLA-A*0201-Restricted CD8+ T Cells in Patients with Melanoma J. Immunol., March 15, 2000; 164(6): 3402 - 3412. [Abstract] [Full Text] [PDF]
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G. Wang, J. Zabner, C. Deering, J. Launspach, J. Shao, M. Bodner, D. J. Jolly, B. L. Davidson, and P. B. McCray Jr. Increasing Epithelial Junction Permeability Enhances Gene Transfer to Airway Epithelia In Vivo Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 129 - 138. [Abstract] [Full Text]
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D. J. Von Seggern, S. Huang, S. K. Fleck, S. C. Stevenson, and G. R. Nemerow Adenovirus Vector Pseudotyping in Fiber-Expressing Cell Lines: Improved Transduction of Epstein-Barr Virus-Transformed B Cells J. Virol., January 1, 2000; 74(1): 354 - 362. [Abstract] [Full Text]
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R. W. Walters, D. Duan, J. F. Engelhardt, and M. J. Welsh Incorporation of Adeno-Associated Virus in a Calcium Phosphate Coprecipitate Improves Gene Transfer to Airway Epithelia In Vitro and In Vivo J. Virol., January 1, 2000; 74(1): 535 - 540. [Abstract] [Full Text]
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J. Zabner, M. Chillon, T. Grunst, T. O. Moninger, B. L. Davidson, R. Gregory, and D. Armentano A Chimeric Type 2 Adenovirus Vector with a Type 17 Fiber Enhances Gene Transfer to Human Airway Epithelia J. Virol., October 1, 1999; 73(10): 8689 - 8695. [Abstract] [Full Text] [PDF]
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C. J. Cohen, J. Gaetz, T. Ohman, and J. M. Bergelson Multiple Regions within the Coxsackievirus and Adenovirus Receptor Cytoplasmic Domain Are Required for Basolateral Sorting J. Biol. Chem., June 29, 2001; 276(27): 25392 - 25398. [Abstract] [Full Text] [PDF]
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C. J. Cohen, J. T. C. Shieh, R. J. Pickles, T. Okegawa, J.-T. Hsieh, and J. M. Bergelson The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction PNAS, December 18, 2001; 98(26): 15191 - 15196. [Abstract] [Full Text] [PDF]
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L. S. Ostedgaard, J. Zabner, D. W. Vermeer, T. Rokhlina, P. H. Karp, A. A. Stecenko, C. Randak, and M. J. Welsh CFTR with a partially deleted R domain corrects the cystic fibrosis chloride transport defect in human airway epithelia in vitro and in mouse nasal mucosa in vivo PNAS, March 5, 2002; 99(5): 3093 - 3098. [Abstract] [Full Text] [PDF]
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