BCCV Gc

BCCV Gc Full Name

Black Creek Canal virus Glycoprotein C

BCCV Gc Introduction

Black Creek Canal virus (BCCV) Gc is the larger of the two surface glycoproteins encoded by the M (medium) RNA segment of BCCV, a New World hantavirus first isolated in 1993 from a fatal case of hantavirus pulmonary syndrome (HPS) in Florida. BCCV is carried by the hispid cotton rat (Sigmodon hispidus) as its natural reservoir host. The Gc glycoprotein (approximately 55 kDa) is generated through post-translational proteolytic cleavage of a common glycoprotein precursor polyprotein, along with its companion glycoprotein Gn. BCCV Gc is a class II transmembrane fusion protein located on the virion surface, anchored via a C-terminal transmembrane domain. It contains conserved fusion peptide motifs and a series of β-sheet-rich domains that undergo conformational changes during membrane fusion. Gc is heavily N-glycosylated, and proper glycosylation is essential for correct folding, intracellular trafficking, and function. Together with Gn, BCCV Gc forms the ordered surface glycoprotein lattice observed on the virion envelope.

Figure 1. Interactions Between Hantavirus Nucleoprotein and Glycoproteins: A Quantitative Fluorescence Microscopy Study.

BCCV Gc plays a critical role in mediating viral entry through pH-dependent membrane fusion within endosomal compartments. Following attachment of the Gn/Gc complex to host cell integrin receptors, particularly αvβ3 integrin expressed on vascular endothelial cells, the virus is internalized via clathrin-mediated endocytosis. The acidic environment of the endosome triggers a dramatic conformational rearrangement in Gc, transitioning from a metastable prefusion dimer to a highly stable post-fusion trimer. This trimerization inserts the fusion peptide into the host endosomal membrane, driving merger of the viral and cellular membranes and release of the viral ribonucleocapsid into the cytoplasm. BCCV Gc is a major target of the host humoral immune response, with neutralizing antibodies primarily directed against conformational epitopes formed by the Gn-Gc heterodimer. Cross-reactivity studies indicate that BCCV Gc shares antigenic determinants with other New World hantaviruses, particularly Bayou virus and Muleshoe virus, consistent with their phylogenetic relatedness. The Gc-mediated fusion mechanism has been extensively studied using pseudotyped vesicular stomatitis virus (VSV) systems expressing BCCV glycoproteins.

The BCCV Gc glycoprotein is a key target for serological diagnostics and vaccine development against HPS caused by New World hantaviruses. Recombinant BCCV Gc expressed in mammalian and baculovirus-insect cell systems has been used to develop ELISA and immunofluorescence assays for detecting Gc-specific antibodies in patient and reservoir surveillance sera. However, compared with more prevalent hantaviruses such as SNV and ANDV, BCCV-specific diagnostics are less widely available. For vaccine development, BCCV Gc has been included in multivalent hantavirus vaccine formulations designed to provide broad protection against multiple New World hantavirus species. DNA vaccines and adenoviral vectors encoding BCCV M segment sequences have shown immunogenicity in preclinical studies. Monoclonal antibodies targeting conserved Gc fusion loop epitopes have demonstrated cross-neutralizing activity against multiple hantaviruses, suggesting a path toward broadly effective immunotherapeutics. Continued characterization of BCCV Gc structure and immunogenicity is essential for understanding the antigenic landscape of North American hantaviruses and developing pan-hantavirus countermeasures.

Alternate Names for BCCV Gc

Black Creek Canal orthohantavirus; Black Creek Canal virus; BCCV; BCCV Glycoprotein C; BCCV Glycoprotein G2; BCCV Gc; BCCV G2

• 1. Hepojoki J et al. Structure and function of the glycoprotein complex of hantaviruses. Viruses. 2020;12(11):1268.
  2. Barriga GP et al. Hantavirus Gc glycoprotein: structure and function as a class II fusion protein. Viruses. 2021;13(5):880.
  3. Song W et al. Receptor binding and membrane fusion mechanisms of New World hantavirus glycoproteins. Journal of Virology. 2019;93(14):e00218-19.
  4. Aji et al. Interactions Between Hantavirus Nucleoprotein and Glycoproteins: A Quantitative Fluorescence Microscopy Study. Viruses. 2025. doi: 10.3390/v17070940