Many virus types are covered by a lipid bilayer. This structure called an envelope, is derived from the host cell and includes host- and virus-encoded proteins. Because envelope components first interact with the host, it is the trigger for infection, immunity and pathology. The roles of especially host-derived constituents are poorly understood. Focusing on herpes simplex type 1 (HSV1) as a model, we have shown that the envelope acquires the physiological initiators of coagulation from the host cell; tissue factor (TF) and procoagulant phospholipid (proPL). Unlike resting cells, where TF and proPL accessibility is carefully restricted, their expression is constitutive on the purified virus enabling factor VIIa (FVIIa)-dependant factor Xa (FXa) and thrombin generation. Interestingly, HSV1-encoded glycoprotein C (gC) on the virus enhances FXa production. In addition to coagulation proteases, HSV1 also facilitates fibrinolytic plasmin generation. HSV1 TF and gC combine to optimally enhance cultured cell infection when both FVIIa and FXa are available through protease activated receptor (PAR) 2. Plasmin also increases infection through PAR2, whereas thrombin provides an additive effect via PAR1. Thus, depending on the host cell, TF and proPL may be a general feature of enveloped viruses, enabling coagulation protease activation and PAR-mediated effects on infection.
Keywords: Coagulation; Envelope; Herpes simplex virus; Protease activated receptor; Tissue factor.
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