Disabling complement regulatory activities of vaccinia virus complement control protein reduces vaccinia virus pathogenicity

• DOI: 10.1016/j.vaccine.2011.07.062
• Publication Date: 2011-08-02T08:51:04Z
• Authors: John Bernet; Muzammil Ahmad; Jayati Mullick; Yogesh Panse; Akhilesh K. Singh; Pradeep B. Parab; Arvind Sahu
• Keywords: Complement control protein; Poxviridae; Decay-accelerating factor; Pathogenesis; Virulence factor

Poxviruses encode a repertoire of immunomodulatory proteins to thwart the host immune system. One among this array is homolog complement regulatory that conserved in various poxviruses including vaccinia (VACV) and variola. The virus control protein (VCP), which inhibits by decaying classical pathway C3-convertase (decay-accelerating activity), supporting inactivation C3b C4b serine protease factor I (cofactor was shown play role viral pathogenesis. However, its individual activities impart pathogenesis, have not yet been elucidated. Here, we generated monoclonal antibodies (mAbs) block VCP functions utilized them evaluate relative contribution pathogenesis employing rabbit intradermal model for VACV infection. Targeting mAbs inhibited decay-accelerating activity as well cofactor or primarily VCP, injecting at site infection, significantly reduced lesion size. This reduction however pronounced when targeted mAb only activity. Further, size reversed depleted cobra venom factor. Thus, our results suggest targeting reduces pathogenicity principally appears contribute virulence.