title: Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor.
abstract: Entry of enveloped viruses into cells is initiated by binding of their envelope glycoproteins (Envs) to cell surface-associated receptors. The Crimean-Congo hemorrhagic fever virus (CCHFV) has two Envs, Gn and Gc, with poorly understood role in binding to susceptible cells. We expressed codon optimized Gn and Gc, and identified independently folded soluble Env fragments, one of which (Gc residues 180-300) bound CCHFV susceptible cells supposedly by interacting with a putative receptor. This receptor binding domain (RBD) was used to identify its interacting partner by coimmunoprecipitation and mass spectrometry. Thus we identified the human cell surface nucleolin as a putative CCHFV entry factor. Nucleolin was expressed on all susceptible cells tested but not on the surface of cells resistant to CCHFV infection. Further studies are needed to explore the nucleolin function as a plausible CCHFV receptor and the molecular mechanisms of the Gc-nucleolin interactions. The identification of the CCHFV RBD and its binding partner could provide novel targets for therapy and tools for prevention as well as more complete understanding of the mechanisms of CCHFV entry and pathogenesis.
authors: Protein Interactions Group, CCR Nanobiology Program, NCI-Frederick, NIH, Frederick, MD 21702, USA.
authors: Xiaodong
authors: X
authors: Xiao
authors: Yang
authors: Y
authors: Feng
authors: Zhongyu
authors: Z
authors: Zhu
authors: Dimiter S
authors: DS
authors: Dimitrov
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization; D000097796:Nucleolin
chemical_list: D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014759:Viral Envelope Proteins; D000097796:Nucleolin