This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Harwood, L. J.
Right arrow Articles by McCullough, K. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Harwood, L. J.
Right arrow Articles by McCullough, K. C.

 Previous Article  |  Next Article 

Journal of Virology, July 2008, p. 6379-6394, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00021-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Dendritic Cell Internalization of Foot-and-Mouth Disease Virus: Influence of Heparan Sulfate Binding on Virus Uptake and Induction of the Immune Response{triangledown}

Lisa J. Harwood,1* Heidi Gerber,1 Francisco Sobrino,2,3 Artur Summerfield,1 and Kenneth C. McCullough1

Institute of Virology and Immunoprophylaxis, 3147 Mittelhäusern, Switzerland,1 Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Cantoblanco, Madrid, Spain,2 Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain3

Received 4 January 2008/ Accepted 2 April 2008

Dendritic cells (DC), which are essential for inducing and regulating immune defenses and responses, represent the critical target for vaccines against pathogens such as foot-and-mouth disease virus (FMDV). Although it is clear that FMDV enters epithelial cells via integrins, little is known about FMDV interaction with DC. Accordingly, DC internalization of FMDV antigen was analyzed by comparing vaccine virus dominated by heparan sulfate (HS)-binding variants with FMDV lacking HS-binding capacity. The internalization was most efficient with the HS-binding virus, employing diverse endocytic pathways. Moreover, internalization relied primarily on HS binding. Uptake of non-HS-binding virus by DC was considerably less efficient, so much so that it was often difficult to detect virus interacting with the DC. The HS-binding FMDV replicated in DC, albeit transiently, which was demonstrable by its sensitivity to cycloheximide treatment and the short duration of infectious virus production. There was no evidence that the non-HS-binding virus replicated in the DC. These observations on virus replication may be explained by the activities of viral RNA in the DC. When DC were transfected with infectious RNA, only 1% of the translated viral proteins were detected. Nevertheless, the transfected cells, and DC which had internalized live virus, did present antigen to lymphocytes, inducing an FMDV-specific immunoglobulin G response. These results demonstrate that DC internalization of FMDV is most efficient for vaccine virus with HS-binding capacity, but HS binding is not an exclusive requirement. Both non-HS-binding virus and infectious RNA interacting with DC induce specific immune responses, albeit less efficiently than HS-binding virus.

* Corresponding author. Mailing address: Institute of Virology and Immunoprophylaxis, CH-3147 Mittelhäusern, Switzerland. Phone: 41-31-848-9319. Fax: 41-31-848-9222. E-mail: Lisa.Harwood{at}ivi.admin.ch

{triangledown} Published ahead of print on 30 April 2008.

Journal of Virology, July 2008, p. 6379-6394, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00021-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»