Tissue Factor Dependent Initiation of Coagulation

on the Surface of HIV

Henry E. 2,3
West ,
Bryan H. J. 2,3
Lin ,
Michael R. 1,2,3
Sutherland ,
4
Ivan Sadowski , and Edward L. G. Pryzdial 1,2,3

Canadian Blood Services Centre for Innovation1, Centre for Blood Research2, Department of Pathology and Laboratory
Medicine3, Department of Biochemistry and Molecular Biology4, University of British Columbia, Vancouver, BC, Canada

BACKGROUND

HYPOTHESES
Tissue factor (TF) is present
on the envelope of cultured
HIV.
Cultured HIV is able to
enhance FVIIa-mediated FXa
generation in a TF dependent
manner.
Cultured HIV initiates plasma
clotting in a TF-like FVIIa
dependant manner

HIV mediates activation of Factor X to Xa in a

RESULTS concentration dependent manner. This reaction
was shown to be TF-dependent through the use of
Immunogold electron microscopy was used to anti-TF antibodies and NapC2.
show the presence of TF on the surface of
10.0 4.0
propagated and purified HSV1 and DENV
FXa Generation

7.5 3.0
(nM)

HSV1 DENV 5.0 2.0

2.5 1.0
gC TF 0.0
TF E 0.0
0.0 25.0 50.0 75.0 100.0
HIV Dilution (%)

HIV initiates plasma clotting. This reaction was

shown to be TF-dependent through the use of anti-
TF antibodies and NapC2. Contribution by the
aPL
Intrinsic Pathway was excluded by using FVII
deficient plasma.
600
Clotting Time (sec)

CONCLUSIONS 400

Evidence suggests the envelope of HIV contains TF and

200
aPL, but the investigation is ongoing.
HIV enhances FXa generation and plasma clotting in a TF-
like FVIIa-dependant manner. 0
HIV No HIV NAPc2 αTF FVIII Def.
Possible mechanistic explanation for thrombotic Plasma
pathologies associated with HIV infections.
This supports TF as a potential target for the development
CBR
of a broad spectrum antiviral. UBC Centre
for
Blood
Research