Koi herpesvirus encodes and expresses a functional interleukin-10

Koi herpesvirus (KHV; species Cyprinid herpesvirus 3) ORF134 was shown to transcribe a spliced transcript encoding a 179 aa IL-10 homolog (khvIL-10) in koi fin (KF-1) cells. Pair-wise sequence alignment indicated that the expressed product shares 25% identity with carp IL-10, 22-24% identity with mammalian (including primate) IL-10s and 19.1% identity with European eel herpesvirus IL-10 (ahvIL-10). In phylogenetic analyses, khvIL-10 fell in a divergent position from all host IL-10 sequences indicating extensive structural divergence following capture from the host. In KHV-infected fish, khvIL-10 transcripts were observed to be highly expressed during the acute and reactivation phases but at a very low level during low-temperature-induced persistence. Similarly, KHV early (Hel and DNAP) and late (ITP and MCP) genes were also expressed at high levels during the acute and reactivation phases but only low level expression of the ITP gene was detected during the persistent phase. Injection of khvIL-10 mRNA into zebrafish (Danio rerio) embryos increased the number of lysozyme-positive cells to a similar degree as zebrafish IL-10. Downregulation of the IL-10 receptor long chain (IL-10R1) using a specific morpholino abrogated the response to both khvIL-10 and zebrafish IL-10 transcripts indicating that, despite the structural divergence, khvIL-10 functions via this receptor. This is the first report describing the characteristics of a functional viral IL-10 gene in the Alloherpesviridae.