Foot-and-mouth disease virus infection in fetal lambs: Tissue tropism and cytokine response

Foot-and-mouth disease virus (FMDV) can cause transplacental infection and death in fetal lambs. This study investigates the pathogenesis of FMDV infection in ovine fetuses using in-situ hybridization (ISH) to detect viral transcripts in tissue and real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays to quantify the fetal cytokine response to infection. FMDV ribonucleic acid (RNA) was localized mainly to the heart and skeletal muscles of fetuses and was only occasionally expressed in the lingual epithelium, demonstrating that FMDV has a different tissue tropism in the fetus compared with that in adult sheep. There was early expression of genes encoding anti-viral cytokines (IFN-alpha and IFN-beta) in fetuses at 2 and 4 days post-infection (dpi), followed by a marked rise in the transcription of pro-inflammatory cytokine genes (IFN-gamma, TNF-alpha and IL-1 alpha) from 7 to 18 dpi, particularly in the heart. The degree of cytokine mRNA expression correlated with fetal infection and was likely to be a factor in fetal death. In contrast, cytokine gene expression in infected neonatal lambs was much less and mainly occurred between 2 and 4 dpi. This study identifies two key factors in the pathogenicity of FMDV in fetal lambs: viral tropism for cardiac and skeletal muscles, and a marked cytokine response following infection.