Foot-and-mouth disease (FMD) is caused by the foot-and-mouth disease virus
(FMDV), genus Aphthovirus, family Picornaviridae. It is a highly contagious disease
of cloven-hoofed animals, has a worldwide distribution and plays an important role in
the limitation of international trade in livestock and livestock products.
The main objectives of this project were to provide an accurate quantitative
description, and develop a mathematical model, of FMDV dynamics in infected pigs.
Time-course studies were set up and the viral load in serum, nasal swabs and tissue
samples were determined. Time after infection, mode of infection, inoculation dose
and housing conditions were examined as possible determinants of viral load.
Similar results were obtained from pigs infected with FMDV by the intravenous,
intradermal or oro-nasal route, i) A strong relationship between inoculation dose and
incubation period of FMDV was evident: the higher the inoculation dose, the shorter
the incubation period, and vice versa, ii) The higher the inoculation dose, the more
predictable and consistent was the incubation period and time-course of infection. The
lower the inoculation dose, the more variable was the incubation period and the
probability of subclinical infections, iii) Housing pigs in a group (rather than
individually) resulted in synchronous infections and reduced the variance in the
incubation period.
Initial models of the early viral dynamics of FMDV disagreed with the experimental
data. Experimental data showed larger effects of dose on the temporal distribution of
viraemia than was predicted by the models. This disagreement could be resolved by:
i) limiting the rate of infection of epithelial cells at low FMDV concentrations; ii)
converting the virus removal system (such as the mononuclear phagocyte system) into
one of limited capacity; or iii) the addition of a virus removal system of limited
capacity, such as non-specific binding of FMDV into the models.
A hypothesis in which the rate of infection of epithelial cells was limited at low
FMDV concentration could be supported by the literature. For FMDV to successfully
infect and replicate within a cell, host protein synthesis has to be inhibited and anti¬
viral defences inactivated. The probability of a successful infection of a cell increases
as the number of infecting viruses increases, suggesting that the rate of infection of
cells at low FMDV concentrations is indeed limited.
The experimental work has highlighted the strong relationship between inoculation
dose and dynamics of FMDV in vivo and the modelling exercise has highlighted
important determinants of viral dynamics, as well as areas where further research
should be directed. This has lead to a deeper understanding of the dynamics of, not
only FMDV, but virus infections in general.
