Orf virus interferes with MHC class I surface expression by targeting vesicular transport and Golgi.
BACKGROUND
The Orf virus (ORFV), a zoonotic Parapoxvirus, causes pustular skin lesions in small ruminants (goat and sheep). Intriguingly, ORFV can repeatedly infect its host, despite the induction of a specific immunity. These immune modulating and immune evading properties are still unexplained.


RESULTS
Here, we describe that ORFV infection of permissive cells impairs the intracellular transport of MHC class I molecules (MHC I) as a result of structural disruption and fragmentation of the Golgi apparatus. Depending on the duration of infection, we observed a pronounced co-localization of MHC I and COP-I vesicular structures as well as a reduction of MHC I surface expression of up to 50%. These subversion processes are associated with early ORFV gene expression and are accompanied by disturbed carbohydrate trimming of post-ER MHC I. The MHC I population remaining on the cell surface shows an extended half-life, an effect that might be partially controlled also by late ORFV genes.


CONCLUSIONS
The presented data demonstrate that ORFV down-regulates MHC I surface expression in infected cells by targeting the late vesicular export machinery and the structure and function of the Golgi apparatus, which might aid to escape cellular immune recognition.
Department of Immunology, Interfaculty Institute for Cell Biology, University of Tuebingen, Tuebingen, Germany.
Jörg
J
Rohde
Frederic
F
Emschermann
Michael R
MR
Knittler
Hanns-Joachim
HJ
Rziha
D000818:Animals; D000911:Antibodies, Monoclonal; D002522:Chlorocebus aethiops; D004474:Ecthyma, Contagious / Q000821:virology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D005805:Genes, MHC Class I / Q000235:genetics / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology*; D009923:Orf virus / Q000502:physiology*; D021381:Protein Transport; D014709:Vero Cells
D000911:Antibodies, Monoclonal