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Prothrombinase assembly on an enveloped virus: evidence that the
cytomegalovirus surface contains procoagulant phospholipid
EL Pryzdial and JF Wright
Research Department, Canadian Red Cross Society, Ottawa.
In contrast to quiescent cells, we currently report that purified
cytomegalovirus (CMV), strain AD169, constitutively expresses
phosphatidylserine (PS)-like procoagulant activity. Initial evidence for
this came from the observation of a CMV-dependent decrease in factor Xa
clotting times. In a purified system, the assembly of a functional complex
between factor Xa and the cofactor Va to form prothrombinase was found to
be dependent on the addition of CMV. The corresponding dense bodies (DB)
and noninfectious enveloped particles had similar activity. Quantification
of the total virion and DB phospholipid, and comparison of prothrombin
conversion rates to experiments conducted using known concentrations of
PS-containing vesicles showed that 8.5% and 7.2% of the CMV and DB
phospholipid, respectively is procoagulant. Direct binding studies of
125I-labeled factor Xa, active site-blocked factor Xa, or the zymogen
factor X, with virions or DB showed a single class of Ca(2+)-dependent
sites with dissociation constants in the order of 10(-7) MOL/l. Immunogold
electron microscopy confirmed the specificity of the CMV/factor Xa
association. Cumulatively, these data suggest that the CMV surface contains
the necessary procoagulant phospholipid for coagulation enzyme complex
assembly. This may enable CMV (and possibly other enveloped viruses) to
bypass an important physiologic regulatory mechanism for the production of
thrombin.
Volume 84,
Issue 11,
pp. 3749-3757,
12/01/1994
Copyright © 1994 by The American Society of Hematology

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