Efficiency of porcine endothelial cell infection with human cytomegalovirus depends on both virus tropism and endothelial cell vascular origin.
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.
Millard
Anne-Laure
AL
Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zürich, Switzerland.
Häberli
Lea
L
Sinzger
Christian
C
Ghielmetti
Maddalena
M
Schneider
Mårten K J
MK
Bossart
Walter
W
Seebach
Jörg D
JD
Mueller
Nicolas J
NJ
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
D000956:Antigens, Viral