Role of the marek’s disease virus (MDV) interleukin-8 (vIL-8) in lymphoma formation and recruitment of target cells

In conclusion, I successfully generated vΔIRL, a novel tool for manipulation of important viral genes such as Meq, vIL-8 or vTR. Furthermore I demonstrated that the secreted vIL-8 chemokine plays an important role in MVD pathogenesis. My data suggest that vIL-8 is involved in various stages of pathogenesis from the establishment of infection to the development of tumors. I identified two novel target cells for vIL-8: B cells, which are the main substrate for lytic replication of MDV, and CD4+CD25+ T cells, a putative target for MDV transformation. My data also indicate that the DKR motif in vIL-8 can be exchanged with ELR without affecting the specificity of vIL-8 to its target cells, supporting the hypothesis that vIL-8 rather a CXCL13 orthologue. Moreover, the vIL-8 C-terminus does not appear to have a major role for the function of vIL-8 as it does not significantly affect MD pathogenesis. In order to generate a markervirus for lytic and latent infection in an oncogenic background to study pathogenesis and tumorigenesis, vUL47-RFP_Meq-GFP was constructed and characterized in vitro and in vivo. Virus replication was not impaired in vitro, however this markervirus was completely attenuated in vivo. Although vUL47-RFP_Meq-GFP did not meet the expectations of an oncogenic markervirus, it is a suitable candidate to facilitate studying latency in the absence of transformation.