Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence

1 Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK 2 School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland Correspondence Geoffrey L. Smith glsmith{at}imperial.ac.uk Camelpox virus (CMLV) gene 176R encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. In vivo , short and long members of the m-slfn family inhibited T-cell development, whereas in vitro , only short m-slfns caused arrest of fibroblast growth. CMLV 176 protein (v-slfn) is most closely related to short m-slfns; however, when expressed stably in mammalian cells, v-slfn did not inhibit cell growth. v-slfn is a predominantly cytoplasmic 57 kDa protein that is expressed throughout infection. Several other orthopoxviruses encode v-slfn proteins, but the v-slfn gene is fragmented in all sequenced variola virus and vaccinia virus (VACV) strains. Consistent with this, all 16 VACV strains tested do not express a v-slfn detected by polyclonal serum raised against the CMLV protein. In the absence of a small animal model to study CMLV pathogenesis, the contribution of CMLV v-slfn to orthopoxvirus virulence was studied via its expression in an attenuated strain of VACV. Recombinant viruses expressing wild-type v-slfn or v-slfn tagged at its C terminus with a haemagglutinin (HA) epitope were less virulent than control viruses. However, a virus expressing v-slfn tagged with the HA epitope at its N terminus had similar virulence to controls, implying that the N terminus has an important function. A greater recruitment of lymphocytes into infected lung tissue was observed in the presence of wild-type v-slfn but, interestingly, these cells were less activated. Thus, v-slfn is an orthopoxvirus virulence factor that affects the host immune response to infection. Present address: Division of Cell and Molecular Biology, Faculty of Natural Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, Exhibition Road, London SW7 2AZ, UK. Present address: Pathology, B23, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium. Supplementary figures are available with the online version of this paper.