The alphaherpesvirus, equine herpesvirus type 1 (EHV-1), is a highly prevalent
cause of equine infectious abortion and encephalomyelopathy. These syndromes
have been attributed to ischemic necrosis from thrombosis in placental and
neural vessels, although the mechanisms underlying thrombosis are unknown.
After inhalation, EHV-1 establishes a peripheral blood mononuclear cell-
associated viremia, with monocytes being a target of infection. Monocytes are
also the main source of tissue factor (TF) in diseased states. Since TF is the
primary activator of coagulation, increased monocyte TF expression could be
involved in EHV-1-associated thrombosis. We hypothesized that EHV-1 infection
would induce TF-dependent procoagulant activity in equine monocytes. Monocyte-
enriched fractions of blood were infected with abortigenic (RacL11, NY03) and
neuropathogenic (Ab4) EHV-1 strains. All strains induced procoagulant
activity, to variable degrees, within 1 to 4 h, with maximal activity at 24 h,
after infection. Virus-induced procoagulant activity was similar to that seen
with lipopolysaccharide, a known stimulant of TF-mediated procoagulant
responses. Virus-induced procoagulant activity was factor VIIa-dependent and
temporally associated with TF gene transcription, implicating TF as the main
driver of the activity. Procoagulant activity was mildly decreased (30-40%)
when virus was inactivated by ultraviolet light or when infected cells were
treated with aphidicolin, a virus DNA polymerase inhibitor, suggesting early
events of virus infection (attachment, entry or intracellular trafficking) are
the primary stimulus of procoagulant activity. Our results indicate that EHV-1
rapidly stimulates procoagulant activity in equine monocytes in vitro. The
EHV-1-induced procoagulant activity in monocytes may contribute to clinical
thrombosis in horses with EHV-1 infection