Teratogenicity of the Semliki Forest virus mutant ts22 for the foetal mouse: Induction of skeletal and skin defects

The maximum proportion of skeletal and/or skin defects induced by the Semliki Forest virus (SFV) mutant ts22 in the 17-day-old foetal mouse occurred following infection of the mother at day 10 of pregnancy. The skeletal defects were detected using a combination of Alcian blue staining for cartilage and Alizarin red staining for bone. Using immunogold-silver staining with anti-SFV IgG and in situ hybridization with a cDNA probe to SFV non-structural sequences, we have shown that mesenchymal cells in the dermis and surrounding developing cartilaginous plates were heavily infected in most foetuses at day 17 of pregnancy, following infection of the mother at day 10. Other infected foetal tissues contained less viral antigen and nucleic acid; they included the liver, muscle (including myocardium), lung and kidney. The central nervous system contained only small amounts of viral antigen and nucleic acid. It is proposed that the skeletal and skin defects induced in mouse foetuses by ts22 infection result from the tropism of the virus mesenchymal cells involved in the development of such tissue.