title: Molecular interactions between porcine and human gammaherpesviruses: implications for xenografts?
abstract: BACKGROUND
  Reactivation of latent herpesviruses is an important cause of morbidity and mortality in human transplantation. This issue might be further complicated in the case of xenotransplantation. Zoonotic viruses could reactivate and replicate in the transplanted tissue, and interactions with homologous human viruses could take place. Since the pig is a favoured animal as donor of organs for human transplants, we analysed the possibility of interactions between porcine and human herpesviruses. Porcine lymphotropic herpesvirus 1 (PLHV-1) is a gammaherpesvirus homologous to Epstein-Barr virus (EBV) and to human herpesvirus 8 (HHV-8), is highly prevalent in pigs and is associated to lymphoproliferative disease in immunosuppressed and transplanted miniature swine.
  
  
  METHODS
  The main viral transactivators of PLHV-1, ORF50, ORF57, ORFA6/BZLF1(h), were cloned and tested for their transactivating ability on several EBV and HHV-8 promoters using reporter assays. Also the effects of HHV-8 ORF50, ORF57 and ORFK8 and EBV BRLF1/ R-transactivator (Rta) and BZLF1/ Z-transactivator (Zta) on PLHV-1 lytic promoters were analysed.
  
  
  RESULTS
  Porcine lymphotropic herpesvirus 1 ORF50 upregulated all HHV-8 promoters and PLHV-1 ORFA6/BZLF1(h) transactivated EBV promoters. Furthermore, transfection of PLHV-1 ORF50 into BC-3 cells, latently infected with HHV-8, resulted in HHV-8 reactivation. Likewise, HHV-8 ORF50 and EBV BRLF1/Rta had a strong transactivating effect on PLHV-1 promoters. Also EBV BZLF1/Zta and HHV-8 ORF57 induced PLHV-1 transactivation, but at lower levels.
  
  
  CONCLUSIONS
  The results suggest that reciprocal molecular interactions between human and porcine herpesviruses might occur in vivo, and support the hypothesis that PLHV-1 might have pathogenic relevance in the course of xenotransplantation.
authors.affiliation: Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Santoni
authors.forename: Iris
authors.initials: I
authors.lastname: Lindner
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Caselli
authors.forename: Michael
authors.initials: M
authors.lastname: Goltz
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ehlers
mesh_terms: D000818:Animals; D004854:Herpesvirus 4, Human / Q000235:genetics*; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic / Q000235:genetics; D018144:Rhadinovirus / Q000235:genetics*; D034421:Sus scrofa / Q000276:immunology / Q000821:virology*; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous / Q000009:adverse effects*