Abstract
BackgroundThe 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.ResultsHere, 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.ConclusionsThe 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.
Highlights
The Orf virus (ORFV), a zoonotic Parapoxvirus, causes pustular skin lesions in small ruminants
We took advantage from the Vero cell-adapted ORFV strain D1701-V to analyse virus induced alterations of MHC I surface expression in infected permissive Vero cells. We show that this Parapoxvirus impairs MHC I surface expression by structurally disrupting the Golgi apparatus
Twelve hours post infection about 80% of MHC I was detectable on the cell surface compared to non-infected cells, which was further reduced to 70% at 24 hpi, and to almost 50% at 36 hpi
Summary
The Orf virus (ORFV), a zoonotic Parapoxvirus, causes pustular skin lesions in small ruminants (goat and sheep). ORFV can repeatedly infect its host, despite the induction of a specific immunity. These immune modulating and immune evading properties are still unexplained. The Orf virus (ORFV; Parapoxvirus ovis) is the type species of the Genus Parapoxvirus belonging to the family Poxviridae It is a skin epitheliotropic double-stranded DNA virus that causes pustular skin lesions in sheep and goats, known as contagious ecthyma [1]. It has been previously shown that ORFV encodes immunomodulators like ORFV IL-10, the GM-CSF- and IL-2-inhibitory factor (GIF) or the ORFV chemokine binding protein CBP, which have the ability to inhibit cytokine synthesis of monocytes [4,5,6,7,8] These evasion strategies seem to play an important role in supporting ORFV replication and enabling repeated re-infections
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