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Title: ANALYSIS OF FOOT-AND MOUTH DISEASE VIRUS RECEPTOR EXPRESSION IN TISSUES FROM NORMAL AND INFECTED CATTLE

Author
item ODONNELL, VIVIAN - UNIV. OF CONN.
item Kozer, Amy
item Gregg, Douglas
item Baxt, Barry

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2005
Publication Date: 6/19/2005
Citation: Odonnell, V., Kozer, A.L., Gregg, D.A., Baxt, B. 2005. Analysis of Foot-and Mouth Disease Virus Receptor Expression in Tissues from Normal and Infected Cattle. XIIIth Meeting of the European Study Group for the Molecular Biology of Picornaviruses. p. D12

Interpretive Summary:

Technical Abstract: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals principally affecting cattle, pigs, sheep and goats. One of the prominent characteristics of the disease are the lesions that form in the keratinocyte-containing stratum spinosum layer of the epithelium. It has been demonstrated that foot-and-mouth disease virus(FMDV) uses the alpha V beta 1,alpha V beta 3, alpha V beta 8 integrins as receptors in vitro via a highly conserved arginine-glycine-aspartic acid amino acid sequence motif located within the beta G-beta H loop of VP1. In order to understand the role of FMDV receptors in tissue tropism and pathogenesis of the disease, we have studied the expression of two major FMDV receptors, alpha V beta 3 and alpha V beta 6, in tissues from normal and FMDV-infected cattle. For these experiments, cryosectioned tissues were fixed with acetone, incubated with monoclonal antibodies to alpha V beta 3, alpha V beta 6, or viral capsid proteins, and examined by confocal microscopy. Examination of the distribution of alpha V beta 6 in uninfected bovine tissues, reveals its presence in the epithelial cell layers (stratum basal and stratum spinosum) in tissues that are important sites for FMDV replication (i.e. tongue and coronary band). Examination of alpha V beta 3 in uninfected bovine tissues, showed that the integrin was expressed in the epithelial cell layers and blood vessels, but in tongue it was expressed only in the dermis, associated with blood vessels. Evaluation of the distribution of alpha V beta 6 within tissues from an FMDV-infected bovine at 24 hours post-inoculation, showed that all the cells that expressed detectable levels of FMDV antigen in the epithelial cells were also positive for alpha V beta 6. In the tongue of FMDV-infected animals, alpha V beta 3 expression was not associated with FMDV-positive cells. In contrast, in coronary band, epithelial cells that expressed viral antigen also expressed alpha V beta 3. Thus, the expression of these integrins represents host proteins that contribute to the tropism of the virus for certain tissues and determin the pathogenesis of the virus. Other factors, however, may also play a role determining viral targets in susceptible hosts.