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Journal of Virology, April 2009, p. 2831-2838, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02368-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Usage of Integrin and Heparan Sulfate as Receptors for Mouse Adenovirus Type 1{triangledown}

Sharmila Raman, Tien-Huei Hsu, Shanna L. Ashley, and Katherine R. Spindler*

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48109

Received 14 November 2008/ Accepted 16 January 2009

Adenovirus fiber knobs are the capsid components that interact with binding receptors on cells, while an Arg-Gly-Asp (RGD) sequence usually found in the penton base protein is important for the interaction of most adenoviruses with integrin entry receptors. Mouse adenovirus type 1 (MAV-1) lacks an RGD sequence in the virion penton base protein. We tested whether an RGD sequence found in the MAV-1 fiber knob plays a role in infection. Treatment of cells with a competitor RGD peptide or a purified recombinant RGD-containing fiber knob prior to infection resulted in reduced virus yields compared to those of controls, indicating the importance of the RGD sequence for infection. An investigation of the role of integrins as possible receptors showed that MAV-1 yields were reduced in the presence of EDTA, an inhibitor of integrin binding, and in the presence of anti-{alpha}v integrin antibody. Moreover, mouse embryo fibroblasts that were genetically deficient in {alpha}v integrin yielded less virus, supporting the hypothesis that {alpha}v integrin is a likely receptor for MAV-1. We also investigated whether glycosaminoglycans play a role in MAV-1 infection. Preincubation of MAV-1 with heparin, a heparan sulfate glycosaminoglycan analog, resulted in a decrease in MAV-1 virus yields. Reduced MAV-1 infectivity was also found with cells that genetically lack heparan sulfate or cells that were treated with heparinase I. Cumulatively, our data demonstrate that the RGD sequence in the MAV-1 fiber knob plays a role in infection by MAV-1, {alpha}v integrin acts as a receptor for the virus, and cell surface heparin sulfate glycosaminoglycans are important in MAV-1 infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Michigan Medical School, 1150 W. Medical Center Dr., 6723 Medical Science Bldg. II, Ann Arbor, MI 48109-5620. Phone: (734) 615-2727. Fax: (734) 764-3562. E-mail: krspin{at}umich.edu

{triangledown} Published ahead of print on 28 January 2009.

Journal of Virology, April 2009, p. 2831-2838, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02368-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Robinson, M., Li, B., Ge, Y., Ko, D., Yendluri, S., Harding, T., VanRoey, M., Spindler, K. R., Jooss, K. (2009). Novel Immunocompetent Murine Tumor Model for Evaluation of Conditionally Replication-Competent (Oncolytic) Murine Adenoviral Vectors. J. Virol. 83: 3450-3462 [Abstract] [Full Text]  


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