TCDB is operated by the Saier Lab Bioinformatics Group

1.G.20 The Hantavirus Gc Envelope Fusion Glycoprotein (Gc-EFG) Family 

Hantaviruses cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. The Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins (Barriga et al. 2016). The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Barriga et al. 2016 predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins.

References associated with 1.G.20 family:

Barriga, G.P., F. Villalón-Letelier, C.L. Márquez, E.A. Bignon, R. Acuña, B.H. Ross, O. Monasterio, G.A. Mardones, S.E. Vidal, and N.D. Tischler. (2016). Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc. PLoS Negl Trop Dis 10: e0004799. 27414047
Hulswit, R.J.G., G.C. Paesen, T.A. Bowden, and X. Shi. (2021). Recent Advances in Bunyavirus Glycoprotein Research: Precursor Processing, Receptor Binding and Structure. Viruses 13:. 33672327
Jin, M., J. Park, S. Lee, B. Park, J. Shin, K.J. Song, T.I. Ahn, S.Y. Hwang, B.Y. Ahn, and K. Ahn. (2002). Hantaan virus enters cells by clathrin-dependent receptor-mediated endocytosis. Virology 294: 60-69. 11886265
Pekosz, A., C. Griot, N. Nathanson, and F. Gonzalez-Scarano. (1995). Tropism of bunyaviruses: evidence for a G1 glycoprotein-mediated entry pathway common to the California serogroup. Virology 214: 339-348. 8553534
Plassmeyer, M.L., S.S. Soldan, K.M. Stachelek, J. Martín-García, and F. González-Scarano. (2005). California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry. Virology 338: 121-132. 15923017
Shtanko, O., R.A. Nikitina, C.Z. Altuntas, A.A. Chepurnov, and R.A. Davey. (2014). Crimean-Congo hemorrhagic fever virus entry into host cells occurs through the multivesicular body and requires ESCRT regulators. PLoS Pathog 10: e1004390. 25233119
Suda, Y., S. Fukushi, H. Tani, S. Murakami, M. Saijo, T. Horimoto, and M. Shimojima. (2016). Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system. Arch Virol 161: 1447-1454. 26935918
Xiao, X., Y. Feng, Z. Zhu, and D.S. Dimitrov. (2011). Identification of a putative Crimean-Congo hemorrhagic fever virus entry factor. Biochem. Biophys. Res. Commun. 411: 253-258. 21723257