Article (Scientific journals)
Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence.
Gubser, Caroline; Goodbody, Rory; Ecker, Andrea et al.
2007In Journal of General Virology, 88 (Pt 6), p. 1667-76
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Keywords :
Amino Acid Sequence; Animals; Body Weight; Bronchoalveolar Lavage Fluid/cytology; Cell Cycle Proteins/genetics; Cell Line; Cercopithecus aethiops; Cytoplasm/chemistry; Disease Models, Animal; Female; Humans; Lung/pathology; Lymphocytes/immunology; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Orthopoxvirus/genetics/immunology/pathogenicity; Poxviridae Infections/pathology; Protein Structure, Tertiary; Sequence Homology, Amino Acid; Vaccinia virus/genetics; Variola virus/genetics; Viral Proteins/chemistry/genetics/physiology; Virulence; Virulence Factors/chemistry/genetics/physiology
Abstract :
[en] 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.
Disciplines :
Immunology & infectious disease
Microbiology
Author, co-author :
Gubser, Caroline;  Imperial college, London
Goodbody, Rory
Ecker, Andrea
Brady, Gareth
O'Neill, Luke A J
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Smith, Geoffrey L;  Imperial College, London
Language :
English
Title :
Camelpox virus encodes a schlafen-like protein that affects orthopoxvirus virulence.
Publication date :
2007
Journal title :
Journal of General Virology
ISSN :
0022-1317
eISSN :
1465-2099
Publisher :
Society for General Microbiology, London, United Kingdom
Volume :
88
Issue :
Pt 6
Pages :
1667-76
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Wellcome Trust [GB]
Available on ORBi :
since 14 May 2009

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