Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

The initial binding of CCHFV to the cell surface is mediated by the glycoproteins Gn and/or Gc. However, the details of specific glycoprotein involvement in viral attachment, internalization, and fusion remain unknown. It is suspected that Gc is responsible for binding to the cellular receptors, as monoclonal antibodies targeting Gc can neutralize CCHFV infection of mammalian cells [37] . The Gc of CCHFV is also thought to mediate fusion; the predicted fusion loop of CCHFV [38] shares significant homology with Rift Valley fever virus (RVFV) Gc fusion loop [39] . The cellular receptors required for CCHFV entry have not been identified. A functional interaction has been suggested between CCHFV Gc and cell surface nucleolin, a protein found predominantly within nucleoli [40] . Nucleolin serves as a receptor for the respiratory syncytial virus, functions as an entry factor for Japanese encephalitis virus, and enhances entry of human immunodeficiency virus (HIV) [41] [42] [43] [44] . However, further investigations in the context of CCHFV infection are needed to support the involvement of nucleolin in CCHFV cell binding and/or fusion.