Foot-and-mouth disease (FMD) is a highly contagious, economically important virus disease of cloven-hoofed animals. The objective of the present study was to examine the early pathogenesis of FMD in pigs by a quantitative time-course study. Under experimental conditions, recipient pigs were infected by contact with donor pigs affected by FMD. Every 24 h from day 1 to day 4 after exposure, two recipient pigs were selected randomly, killed and necropsied. A range of tissues were analysed by a quantitative TaqMan RT–PCR method and by titration of FMD virus on primary bovine thyroid cells. The titres of virus determined by assay in cell culture and calculated from the quantitative TaqMan data correlated strongly (r>0·9), thereby establishing the validity of the TaqMan calculations. The data indicated that the replication of virus in the lungs contributes only in small part to airborne virus excretion. Sites in the pharynx, trachea and nasal mucosa are probably more important in that regard. The sites of earliest virus infection and possibly replication in recipient pigs appeared to be in the pharynx (soft palate, tonsil and floor of pharynx). The data indicated that FMD virus replication in pigs is rapid and that the majority of virus amplification occurs in the skin. A model for the progression of infection is proposed, indicating initial spread from the pharyngeal region, through regional lymph nodes and via the blood to epithelial cells, resulting in several cycles of virus amplification and spread.
AlexandersenS.,
BloomM. E.,
WolfinbargerJ.1988; Evidence of restricted viral replication in adult mink infected with Aleutian disease of mink parvovirus. Journal of Virology 62:1495–1507
AlexandersenS.,
ForsythM. A.,
ReidS. M.,
BelshamG. J.2000; Development of reverse transcription–PCR (oligonucleotide probing) enzyme-linked immunosorbent assays for diagnosis and preliminary typing of foot-and-mouth disease: a new system using simple and aqueous-phase hybridization. Journal of Clinical Microbiology 38:4604–4613
AusubelF. M.,
BrentR.,
KingstonR. E.,
MooreD. D.,
SeidmanJ. G.,
SmithJ. A.StruhlK.
(editors) 1988Current Protocols in Molecular Biology New York: Wiley;
BelshamG. J.1993; Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure. Progress in Biophysics & Molecular Biology 60:241–260
BurrowsR.,
MannJ. A.,
GarlandA. J.,
GreigA.,
GoodridgeD.1981; The pathogenesis of natural and simulated natural foot-and-mouth disease infection in cattle. Journal of Comparative Pathology 91:599–609
DavidsonF. L.1997; Alternative strategies for foot-and-mouth disease control in pigs. PhD thesis University of Hertfordshire; UK:
De CastroM. P.1964; Behaviour of the foot and mouth disease virus in cell cultures: susceptibility of the IB-RS-2 cell line. Arquivos do Instituto Biologico Sao Paulo 31:63–78
DonaldsonA. I.1986; Aerobiology of foot-and-mouth disease (FMD): an outline and recent advances. Revue Scientifique et Technique Office International des Epizooties 5:315–321
DonaldsonA. I.,
FerrisN. P.1980; Sites of release of airborne foot-and-mouth disease virus from infected pigs. Research in Veterinary Science 29:315–319
DonaldsonA. I.,
HernimanK. A.,
ParkerJ.,
SellersR. F.1970; Further investigations on the airborne excretion of foot-and-mouth disease virus. Journal of Hygiene 68:557–564
DonaldsonA. I.,
GarlandA. J.,
FerrisN. P.,
CollenT.1981; The 1975 foot-and-mouth disease epidemic in Malta. I: Experimental studies with the causal virus strain O1 Malta. British Veterinary Journal 137:300–307
DonaldsonA. I.,
GlosterJ.,
HarveyL. D.,
DeansD. H.1982; Use of prediction models to forecast and analyse airborne spread during the foot-and-mouth disease outbreaks in Brittany, Jersey and the Isle of Wight in 1981. Veterinary Record 110:53–57
DonaldsonA. I.,
GibsonC. F.,
OliverR.,
HamblinC.,
KitchingR. P.1987; Infection of cattle by airborne foot-and-mouth disease virus: minimal doses with O1 and SAT 2 strains. Research in Veterinary Science 43:339–346
DonaldsonA. I.,
KitchingP.,
BarnettI. T.1996; Foot-and-mouth disease. In Manual of Standards for Diagnostic Tests and Vaccines pp 47–56 Paris: Office International des Epizooties;
FerrisN. P.,
DawsonM.1988; Routine application of enzyme-linked immunosorbent assay in comparison with complement fixation for the diagnosis of foot-and-mouth and swine vesicular diseases. Veterinary Microbiology 16:201–209
FerrisN. P.,
PowellH.,
DonaldsonA. I.1988; Use of pre-coated immunoplates and freeze-dried reagents for the diagnosis of foot-and-mouth disease and swine vesicular disease by enzyme-linked immunosorbent assay (ELISA. Journal of Virological Methods 19:197–206
HamblinC.,
ArmstrongR. M.,
HedgerR. S.1984; A rapid enzyme-linked immunosorbent assay for the detection of foot-and-mouth disease virus in epithelial tissues. Veterinary Microbiology 9:435–443
HamblinC.,
BarnettI. T.,
HedgerR. S.1986a; A new enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against foot-and-mouth disease virus. I. Development and method of ELISA. Journal of Immunological Methods 93:115–121
HamblinC.,
BarnettI. T.,
CrowtherJ. R.1986b; A new enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against foot-and-mouth disease virus. II. Application. Journal of Immunological Methods 93:123–129
HatchT. F.,
GrossP.1964Pulmonary Deposition and Retention of Inhaled Aerosols pp 45–68 London: Academic Press;
LennetteE. H.1964Diagnostic Procedures for Viral and Rickettsial Diseases pp 48–51 New York: American Public Health Association;
ManiatisT.,
FritschE. F.,
SambrookJ.1982Molecular Cloning: A Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
OleksiewiczM. B.,
DonaldsonA. I.,
AlexandersenS.2001; Development of a real-time RT–PCR assay for quantitation of foot-and-mouth disease virus in diverse porcine tissues. Journal of Virological Methods 92:23–35
RoederP. L.,
Le Blanc SmithP. M.1987; Detection and typing of foot-and-mouth disease virus by enzyme-linked immunosorbent assay: a sensitive, rapid and reliable technique for primary diagnosis. Research in Veterinary Science 43:225–232
SaltJ. S.,
BarnettP. V.,
DaniP.,
WilliamsL.1998; Emergency vaccination of pigs against foot-and-mouth disease: protection against disease and reduction in contact transmission. Vaccine 16:746–754