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structural proteins; secreted NS1 was
found only in supernatants from infected Vero cells.
Using supernatant culture fluids from [35S]methionine-
labelled, virus-infected Vero and C6/36 cells, binding
of radiolabelled viral proteins was examined with various
cell lines varying in susceptibility to DEN-4 infection.
Binding of viral E protein was observed with the highly
infectible Vero and LLC-MK2 cell lines, whereas a very
small degree of binding was seen with four other cell
lines (mouse fibroblast L929, bovine kidney MDBK, human
hepatoma Hep G2 and primary human endothelial cells)
which are less susceptible to DEN-4 infection. The results
suggest that cell susceptibility to DEN-4 may be determined
largely at the stage of virus binding, i.e. by the presence
of a cell receptor capable of binding viral E protein.
Anderson, R., S. Wang, et al. (1997).
"Activation of endothelial cells via antibody-enhanced
dengue virus infection of peripheral blood monocytes."
J.Virol. 71(6): 4226-32.
Although endothelial cells have been speculated to be
a target in the pathogenesis of dengue hemorrhagic fever
(DHF), there has been little evidence linking dengue
virus infection to any alteration in endothelial cell
function. In this study, we show that human umbilical
vein endothelial cells become activated when exposed
to culture fluids from dengue virus-infected peripheral
blood monocytes. Maximum activation was achieved with
culture fluids from monocytes in which virus infection
was enhanced by the addition of dengue virus-immune
serum, thus correlating with epidemiological evidence
that prior immunity to dengue virus is a major risk
factor for DHF. Activation was strongest for endothelial
cell expression of VCAM-1 and ICAM-1. In contrast, activation
of endothelial cell E-selectin expression appeared to
be more transient, as indicated by its detection at
3 h, but not at 16 h, of treatment. Treatment of monocyte
culture fluids with anti-tumor necrosis factor alpha
(TNF-alpha) antibody largely abolished the activation
effect (as measured by endothelial cell expression of
ICAM-1), whereas treatment with IL-1beta receptor antagonist
had a much smaller inhibitory effect on activation.
Endothelial cells inoculated directly with dengue virus
or with virus-antibody combinations were poorly infectable
(compared to Vero cells or peripheral blood monocytes),
and virus-inoculated endothelial cells showed no increased
expression of VCAM-1, ICAM-1, or E-selectin. Taken together,
the results strongly indicate that dengue virus can
modulate endothelial cell function by an indirect route,
in which a key intermediary is TNF-alpha released from
virus-infected monocytes.
Andis, M. D., S. R. Sackett, et al.
(1987). "Strategies for the emergency control of
arboviral epidemics in New Orleans." J.Am.Mosq.Control.Assoc.
3: 125-130.
Andrei, G. and E. De Clercq (1993).
"Molecular approaches for the treatment of hemorrhagic
fever virus infections." Antiviral Res. 22: 45-75.
AD: Rega Institute for Medical Research, Katholieke
Universiteit Leuven, Belgium AB: Viruses causing hemorrhagic
fevers in man belong to the following virus groups:
togavirus (Chikungunya), flavivirus (dengue, yellow
fever, Kyasanur Forest disease, Omsk hemorrhagic fever),
arenavirus (Argentinian hemorrhagic fever, Bolivian
hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg),
phlebovirus (Rift Valley fever), nairovirus (Crimian-
Congo hemorrhagic fever) and hantavirus (hemorrhagic
fever with renal syndrome, nephropathic epidemia). Hemorrhagic
fever virus infections
 
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