Open AccessFoot-and-mouth disease virus non-structural protein 3A modulates cellular innate immune responses to influence host tropism
Author(s) -
Soumendu Chakravarti,
Caroline F. Wright,
Emma Howes,
Richard Kock,
Terry Jackson,
Toby Tuthill
Publication year - 2020
Publication title -
access microbiology
Language(s) - English
Resource type - Journals
ISSN - 2516-8290
DOI - 10.1099/acmi.ac2020.po0377
Subject(s) - virology , picornavirus , biology , tropism , tissue tropism , virus , interferon , foot and mouth disease virus , immune system , innate immune system , viral replication , gene , genome , genetics
The picornavirus foot-and-mouth disease virus (FMDV) is responsible for one of the most significant diseases of livestock, leading to large economic losses due to reduced productivity and trade embargoes for areas not certified as disease-free. The picornavirus non-structural protein 3A is involved in replication of the viral RNA genome and is implicated in host tropism of several picornaviruses. Deletions in the C-terminus of 3A have been observed in FMDV outbreaks specific for swine and such viruses are non-pathogenic in cattle. The mechanism for species specific attenuation of FMDV is unknown. We have shown that FMDV containing a C-terminal deletion in 3A is attenuated in bovine cell culture and that the attenuated phenotype can be reversed by the JAK1/2 inhibitor Ruxolitinib (Rux), identifying a role for the induction of interferon stimulated genes (ISGs) in the restricted bovine tropism of the 3A-deleted virus.