OATAO - Open Archive Toulouse Archive Ouverte Open Access Week

Tolerance to mutations in the foot-and-mouth disease virus integrin-binding RGD region is different in cultured cells and in vivo and depends on the capsid sequence context.

Gutiérrez-Rivas, Monica and Pulido, Miguel R and Baranowski, Eric and Sobrino, Francisco and Sáiz, Margarita Tolerance to mutations in the foot-and-mouth disease virus integrin-binding RGD region is different in cultured cells and in vivo and depends on the capsid sequence context. (2008) Journal of General Virology, 89 (10). pp. 2531-2539. ISSN 0022-1317

[img] (Document in English)

PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
177kB

Official URL: http://vir.sgmjournals.org/cgi/reprint/89/10/2531.pdf

Abstract

Engineered RNAs carrying substitutions in the integrin receptor-binding Arg-Gly-Asp (RGD) region of foot-and-mouth disease virus (FMDV) were constructed (aa 141-147 of VP1 capsid protein) and their infectivity was assayed in cultured cells and suckling mice. The effect of these changes was studied in the capsid proteins of two FMDVs, C-S8c1, which enters cells through integrins, and 213hs(-), a derivative highly adapted to cell culture whose ability to infect cells using the glycosaminoglycan heparan sulfate (HS) as receptor, acquired by multiple passage on BHK-21 cells, has been abolished. The capsid sequence context determined infectivity in cultured cells and directed the selection of additional replacements in structural proteins. Interestingly, a viral population derived from a C-S8c1/L144A mutant, carrying only three substitutions in the capsid, was able to expand tropism to wild-type (wt) and mutant (mt)glycosaminoglycan-deficient CHO cells. In contrast, the 213hs(-) capsid tolerated all substitutions analysed with no additional mutations, and the viruses recovered maintained the ability of the 213hs(-) parental virus to infect wt and mt CHO cells. Viruses derived from C-S8c1 with atypical RGD regions were virulent and transmissible for mice with no other changes in the capsid. Substitution of Asp143 for Ala in the C-S8c1 capsid eliminated infectivity in cultured cells and mice. Co-inoculation with a neutralizing monoclonal antibody directed against the type C FMDV RGD region abolished infectivity of C-S8c1 virus on suckling mice, suggesting that FMDV can infect mice using integrins. Sequence requirements imposed for viral entry in vitro and in vivo are discussed.

Item Type:Article
Additional Information:Thanks to the Society for General Microbiology. The definitive version is available at http://vir.sgmjournals.org/. The original PDF of the article can be found at Journal of General Virology website: http://vir.sgmjournals.org/cgi/reprint/89/10/2531.pdf
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:Other partners > Consejo Superior de Investigaciones Científicas - CSIC (SPAIN)
Université de Toulouse > Ecole Nationale Vétérinaire de Toulouse - ENVT
French research institutions > Institut National de la Recherche Agronomique - INRA
Other partners > Instituto Nacional de Investigacion y Tecnologia Agraria y Alimentaria (SPAIN)
Other partners > Universidad Autonoma de Madrid (SPAIN)
Laboratory name:
Statistics:download
Deposited By: Eric Baranowski

Repository Staff Only: item control page