Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence.
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.
Gubser
Caroline
C
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Goodbody
Rory
R
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Ecker
Andrea
A
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Brady
Gareth
G
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
O'Neill
Luke A J
LAJ
School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Jacobs
Nathalie
N
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Smith
Geoffrey L
GL
Department of Virology, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
D000595:Amino Acid Sequence; D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018155:Orthopoxvirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D011213:Poxviridae Infections / Q000473:pathology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014616:Vaccinia virus / Q000235:genetics; D012901:Variola virus / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D014764:Viral Proteins; D037521:Virulence Factors; C504818:schlafen-1 protein, mouse