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Müller, Silvia (2008): Untersuchungen über den Einfluss des Equiden Herpesvirus 1 auf die MHC I- und MHC II-Expression equiner Zellen. Dissertation, LMU München: Tierärztliche Fakultät



Analysis of MHC I and II presentation on Equid herpesvirus 1 infected cells Various Alphaherpesviruses are able to interfere with MHC class I presentation by reducing surface expression of these molecules. Equid herpesvirus 1 (EHV-1) infection also results in MHC I downregulation on the respective cells, but other than the involvement of the viral UL49.5-protein, this process is not yet very well understood (Rappocciolo et al., 2003; Ambagala et al., 2004; Koppers-Lalic et al., 2005). As the in vitro non essential EHV-1 proteins UL11p and UL43p were considered as further candidate proteins for playing a role in interfering with MHC I or II expression, the aim of this study was to elucidate this supposition. In a first step, the influence of EHV-1-infection on MHC I/II surface expression had to be investigated. At various time-points p.i., a considerable reduction of MHC class I-molecules on the surface of EHV-1-infected cultured equine cells could indeed be confirmed and was also observed after in vitro-infection of equine PBMC. Moreover, it could be clearly demonstrated for the first time that EHV-1-infection also results in a downregulation of MHC II expression on equine cell culture cells following interferon--induction. MHC II-expression on the surface of in vitro EHV-1-infected PBMC, however, was reduced slightly only. Previous results gave rise to the hypothesis that the EHV-1 proteins UL11p and /or UL43p might be involved in EHV-1-induced immunomodulation. In the course of this study, however, it could be demonstrated that neither a deletion of the UL11- nor of the UL43-gene had an impact on the downregulation of MHC I or II surface expression. No difference in MHC I presentation was detectable between cells infected with the recently isolated EHV-1 strains O834 (myeloencephalopathy, 1999) and E216 (abortion, 2006) but, surprisingly, MHC class I downregulation was even more pronounced than on cells infected with the EHV-1 strain RacL11 (abortion, 1958). The interferon- induced MHC II presentation, however, was affected similarly by all EHV-1 strains tested. Interestingly, during the course of this study, it became obvious that deleting the UL43-gene does not influence MHC I or II surface expression, but the distribution of viral cell surface glycoproteins in EHV-1-infected cells. Comparative studies with cells infected with RacL11, RacH, and the respective UL43-deleted viruses revealed that the absence of the UL43 gene-product resulted in quantitative changes concerning the expression of EHV-1 glycoproteins such as gC, gp2 and gD, as assessed by flow cytometry analysis. In addition, by confocal laser scanning microscopy, clear variations regarding the distribution of gB and gC were shown. Other glycoproteins, such as gM or membrane-associated proteins such as UL11p were not affected. These results give rise to the assumption that UL43p might in fact play a by far more important role in vivo than has yet been demonstrated in vitro.