Differential gene expression in bovine cells infected with wild type and leaderless foot-and-mouth disease virus.
The leader proteinase (L(pro)) of foot-and-mouth disease virus (FMDV) plays a critical role in viral pathogenesis. Molecular studies have demonstrated that L(pro) inhibits translation of host capped mRNAs and transcription of some genes involved in the innate immune response. We have used microarray technology to study the gene expression profile of bovine cells infected with wild type (WT) or leaderless FMDV. Thirty nine out of approximately 22,000 bovine genes were selectively up-regulated by 2 fold or more in leaderless versus WT virus infected cells. Most of the up-regulated genes corresponded to IFN-inducible genes, chemokines or transcription factors. Comparison of promoter sequences suggested that host factors NF-kappaB, ISGF3G and IRF1 specifically contributed to the differential expression, being NF-kappaB primarily responsible for the observed changes. Our results suggest that L(pro) plays a central role in the FMDV evasion of the innate immune response by inhibiting NF-kappaB dependent gene expression.
Zhu
James
J
Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944, USA.
Weiss
Marcelo
M
Grubman
Marvin J
MJ
de los Santos
Teresa
T
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D010450:Endopeptidases / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D057131:Immune Evasion; D007113:Immunity, Innate; D020411:Oligonucleotide Array Sequence Analysis; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D037521:Virulence Factors; D010450:Endopeptidases; C088747:leader proteinase, foot-and-mouth disease virus