A captured viral interleukin 10 gene with cellular exon structure

1 Division of Medical Microbiology, School of Infection and Host Defence, University of Liverpool, Liverpool L69 3GA, UK 2 Moredun Research Institute, Edinburgh EH16 0PZ, UK 3 Medical Research Council Virology Unit, Institute of Virology, University of Glasgow, Glasgow G11 5JR, UK 4 Institute of Virology, University of Zurich, Zurich, Switzerland Correspondence James P. Stewart j.p.stewart{at}liv.ac.uk We have characterized a novel, captured and fully functional viral interleukin (IL)-10 homologue ( OvHV IL-10) from the gammaherpesvirus ovine herpesvirus 2. Unlike IL-10 homologues from other gammaherpesviruses, the OvHV IL-10 peptide sequence was highly divergent from that of the host species. The OvHV IL-10 gene is unique amongst virus captured genes in that it has precisely retained the original cellular exon structure, having five exons of similar sizes to the cellular counterparts. However, the sizes of the introns are dramatically reduced. The OvHV IL-10 protein was shown to be a non-glycosylated, secreted protein of M r 21 000 with a signal peptidase cleavage site between amino acids 26 and 27 of the nascent peptide. Functional assays showed that OvHV IL-10, in a similar way to ovine IL-10, stimulated mast cell proliferation and inhibited macrophage inflammatory chemokine production. This is the first example of a captured herpesvirus gene retaining the full cellular gene structure. Present address: School of Veterinary Medicine and Science, Nottingham University, Sutton Bonington LE12 5RD, UK. The GenBank/EMBL/DDBJ accession number for the ovine IL-10 gene sequence reported in this study is AJ748588. A supplementary table and two supplementary figures are available with the online version of this paper.