Adult human heart microvascular endothelial cells are permissive for non-lytic infection by human cytomegalovirus.
OBJECTIVE
Human cytomegalovirus (CMV) infection has been linked to chronic heart disease. The mechanism of CMV dissemination to the heart remains unknown. CMV antigens and nucleic acid sequences have been detected in endothelial cells (ECs) in vivo, and ECs are fully permissive hosts to CMV replication in vitro. This report examines the characteristics of CMV replication in primary cultures of human heart microvascular ECs (HHMECs).


METHODS
Capillary ECs were isolated from heart tissue biopsies of six patients at the time of heart surgery. HHMECs were infected with CMV and viral antigens were detected by immunofluorescence assay using monoclonal antibodies as specific reagents. Cytokine and chemokine release in the supernatant of sham- and CMV-infected cells was quantitated by ELISA. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyse expression of mRNA for adhesion molecules.


RESULTS
CMV was found to productively infect HHMECs without cytolytic effects. Infected cultures released high levels of pro-inflammatory chemokines and enhanced their adhesion molecule expression.


CONCLUSIONS
Our data provide new insights into the mechanism of CMV dissemination to the heart, signalling the need for further investigation of the pathogenetic role of this virus in cardiac disorders.
Ricotta
D
D
Institute of Microbiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.
Alessandri
G
G
Pollara
C
C
Fiorentini
S
S
Favilli
F
F
Tosetti
M
M
Mantovani
A
A
Grassi
M
M
Garrafa
E
E
Dei Cas
L
L
Muneretto
C
C
Caruso
A
A
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000032:analysis; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology / Q000821:virology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014779:Virus Replication
D000956:Antigens, Viral; D018932:Chemokine CCL2; D019040:E-Selectin; D015850:Interleukin-6; D016209:Interleukin-8; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1