A new member of the interleukin 10-related cytokine family encoded by a poxvirus

Bartlett, NW Dumoutier, Laure [UCL] Renauld, Jean-Christophe [UCL] Kotenko, SV McVey, CE Lee, HJ Smith, GL et al.[show all]

Poxviruses express numerous proteins involved in manipulating the host immune response. Analysis of the primary sequence and predicted structure of the 134R protein of Yaba-like disease virus (Y134R) indicated that it is similar to cellular proteins of the IL-10 family, specifically IL-19, IL-20 and IL-24. A flag-tagged Y134R was expressed from mammalian cells and identified as a secreted, monomeric glycoprotein that stimulated signal transduction from class II cytokine receptors IL-20Ralpha/IL-20Rbeta (IL-20R type1) and IL-22R/IL-20Rbeta (IL-20R type 2). Y134R induced phosphorylation of signal transducers and activators of transcription, their translocation to the nucleus and the induction of reporter gene expression. In contrast, Y134R was unable to induce similar responses from either the IL-22 or IFN-lambda (IL-28A, IL-2813, IL-29) class II cytokine receptors. To examine the role Y134R plays during a poxvirus infection, a vaccinia virus recombinant expressing Y134R was constructed and tested in a murine intranasal infection model. Compared with control viruses, the virus expressing Y134R had a reduced virulence, manifested by reduced weight loss, signs of illness and virus titres in infected organs. These results demonstrate that Y134R is a new viral member of the IL-10-related cytokine family and that its activity in vivo affects virus virulence.