Hantaan virus infection of human endothelial cells.
The primary pathophysiologic finding of the viral disease known as Korean hemorrhagic fever, the etiological agent of which is Hantaan virus (HTV), is vascular instability. To investigate whether HTV was able to infect cells derived from human vascular tissue and alter their behavior, we infected in vitro primary adult human endothelial cells from saphenous veins (HSVEC). We were able to detect the presence of viral antigens in infected cells both by immunofluorescence and by Western blot (immunoblot) analysis as early as day 1 postinfection. HSVEC infected with HTV produce infectious virus during the first 3 days of infection but, at later times (days 4 to 8), show decreasing yields of virus. This contrasts with the HTV growth pattern observed for the permissive simian CV-7 cell line, which generates infectious virus up to day 12 after infection. Further investigation showed that the late decrease in viral production in HSVEC is the result of the induction of beta interferon and can be reversed by the addition of anti-beta interferon serum to the culture medium. At no time during the course of infection of HSVEC with HTV was any obvious cytopathic effect observed. When tests for changes in mRNA levels of other cytokines and endothelial cell gene products following HTV infection of HSVEC were done by reverse transcription and polymerase chain reaction methods, no significant changes were observed in the levels of interleukin 1, interleukin 6, or von Willebrand factor mRNA. We hypothesize that, while HTV can replicate in human vascular endothelial cells, the mechanism of microvascular damage seen with Korean hemorrhagic fever is not likely to be a direct effect of virus replication but may conceivably be the consequence of an immune-mediated endothelial injury triggered by viral infection.
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
M N
MN
Pensiero
J B
JB
Sharefkin
C W
CW
Dieffenbach
J
J
Hay
D000956:Antigens, Viral / Q000032:analysis; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D005455:Fluorescent Antibody Technique; D006476:Orthohantavirus / Q000302:isolation & purification / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000382:microbiology / Q000503:physiopathology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014779:Virus Replication; D014841:von Willebrand Factor / Q000235:genetics
D000956:Antigens, Viral; D007375:Interleukin-1; D015850:Interleukin-6; D009841:Oligonucleotides; D012333:RNA, Messenger; D014841:von Willebrand Factor