title: Efficiency of porcine endothelial cell infection with human cytomegalovirus depends on both virus tropism and endothelial cell vascular origin.
abstract: BACKGROUND
  Human cytomegalovirus (HCMV) infection or reactivation has been linked to allograft rejection resulting from endothelial injury and immune activation. In pig-to-human xenotransplantation, currently investigated to circumvent the shortage of human organs in transplantation medicine, the porcine endothelium will inevitably be exposed to human pathogens such as HCMV. We investigated the susceptibility of porcine endothelial cells (pEC) to HCMV infection.
  
  
  METHODS
  Immortalized porcine aortic (PEDSV15) and porcine microvascular bone-marrow derived EC (2A2) as well as a panel of primary pEC originated from different vascular beds were inoculated with the endotheliotropic (TB40/E) and the fibroblast propagated (TB40/F) HCMV strains at multiplicity of infection (MOI) ranging from 0.1 to 5. Viral replication kinetics, development of cytopathology and release of viral progeny were analyzed.
  
  
  RESULTS
  All viral strains infected pEC with differences in both infection efficiency and kinetics of cytopathology. Moreover, differences in susceptibility of pEC derived from distinct vascular beds were observed. HCMV underwent a complete replication cycle in about 5% of the infected pEC. Comparing the permissiveness of pEC to human aortic EC (HAEC) revealed differences in strain susceptibility and lower rates of late antigen expression in pEC. Finally, HCMV-infected pEC released viral particles but with a lower efficiency than infected HAEC.
  
  
  CONCLUSIONS
  Our data demonstrate that HCMV productively infects pEC, therefore finding strategies to render pEC resistant to HCMV infection will be of interest to reduce the potential risk carried by HCMV reactivation in xenotransplantation.
authors: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zürich, Switzerland.
authors: Anne-Laure
authors: AL
authors: Millard
authors: Lea
authors: L
authors: Häberli
authors: Christian
authors: C
authors: Sinzger
authors: Maddalena
authors: M
authors: Ghielmetti
authors: Mårten K J
authors: MK
authors: Schneider
authors: Walter
authors: W
authors: Bossart
authors: Jörg D
authors: JD
authors: Seebach
authors: Nicolas J
authors: NJ
authors: Mueller
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001011:Aorta / Q000166:cytology / Q000821:virology; D017209:Apoptosis; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D042783:Endothelial Cells / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000821:virology; D006801:Humans; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects; D018523:Tropism; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral