Orf virus interferes with MHC class I surface expression by targeting vesicular transport and Golgi
- Equal contributors
1 Present address: Department of Immunology, Interfaculty Institute for Cell Biology, University of Tuebingen, Auf der Morgenstelle 15, 72076, Tuebingen, Germany
2 Friedrich-Loeffler-Institute, Federal Research Institute of Animal Health, Institute of Immunology, Greifswald-Insel Riems, Germany
BMC Veterinary Research 2012, 8:114 doi:10.1186/1746-6148-8-114Published: 18 July 2012
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.
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.
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.