Arch Virol (2002) 147: 2157–2167
The effects of gamma interferon on replication of foot-and-mouth
disease virus in persistently infected bovine cells
Z. D. Zhang, G. Hutching, P. Kitching, and S. Alexandersen
Pirbright Laboratory, Institute for Animal Health, Pirbright, U.K.
Received June 27, 2001; accepted June 11, 2002
Published online August 19, 2002
Summary. Foot-and-mouth disease virus (FMDV) causes a highly contagious
viral disease of cloven-hoofed animals, which has a considerable socio-economic
impactonthecountriesaffected. Inaddition,persistent infectioncanoccur follow-
ing clinical or sub-clinical disease in either vaccinated or non-vaccinated cattle.
The mechanism(s) by which FMDV persistence is established and maintained
is not fully understood. To better understand the basic mechanisms controlling
the virus infection in cattle, the effects of interferon gamma (IFN-γ)onthe
replication of FMDV was evaluated in vitro in persistently infected-epithelial
cells isolated from FMDV infected cattle. Initially primary bovine thyroid (BTY)
cells were treated with varying doses of bovine recombinant IFN-γ. The cytokine
activity was measured by detection of viral antigen in cell supernatants and viral
RNA expression compared with cells without INF-γ treatment. Pretreatment
with IFN-γ profoundly affected FMDV growth in BTY cells. The replication
of FMDV was affected in the presence of more than 2.5u/ml of IFN-γ and the
effect was both dose-dependent and related to the time of exposure. Analysis
of the mechanism of inhibition suggests that IFN-γ did not inhibit the viral
replication through induction of nitric oxide. More interesting is the ﬁnding that
continuous treatment with IFN-γ severely restricts FMDV replication or even
cures persistently infected bovine epithelial cells, indicating that a cytokine-
mediated pathway may be involved in the in vivo clearance of persistent FMDV.
Foot-and-mouthdisease virus (FMDV) is a member of the family Picornaviridae,
genus Aphthovirus which causes a highly contagious disease in cloven-hoofed
animals characterized by the appearance of vesicles on the feet and mouth .
Of considerable importance in the control of FMD is the persistent infection
that can occur following clinical or sub-clinical disease in both vaccinated and