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Citation: Wei Ye, Chuantao Ye, Yongliang Hu, Yangchao Dong, Yingfeng Lei, Fanglin Zhang. The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed; many more still need an answer [J].VIROLOGICA SINICA, 2022, 37(4) : 634-636.  http://dx.doi.org/10.1016/j.virs.2022.05.003

The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed; many more still need an answer

  • Highlights
    1. The structure of glycoprotein Gc, responsible for mediating membrane fusion between cell and CCHFV, is revealed, but many more mysteries remain.
    2. Why do only antibodies against Gc have neutralizing effect, but not the one against Gn?
    3. Why can NAbs against Gc only be protective in the animals in preventive settings, but not in the therapeutic administration?

  • 加载中
    1. Erickson, B.R., Deyde, V., Sanchez, A.J., Vincent, M.J., Nichol, S.T., 2007. N-linked glycosylation of gn (but not gc) is important for crimean Congo hemorrhagic fever virus glycoprotein localization and transport. Virology 361, 348–355.

    2. Fels, J.M., Maurer, D.P., Herbert, A.S., Wirchnianski, A.S., Vergnolle, O., Cross, R.W., Abelson, D.M., Moyer, C.L., Mishra, A.K., Aguilan, J.T., Kuehne, A.I., Pauli, N.T., Bakken, R.R., Nyakatura, E.K., Hellert, J., Quevedo, G., Lobel, L., Balinandi, S., Lutwama, J.J., Zeitlin, L., Geisbert, T.W., Rey, F.A., Sidoli, S., McLellan, J.S., Lai, J.R., Bornholdt, Z.A., Dye, J.M., Walker, L.M., Chandran, K., 2021. Protective neutralizing antibodies from human survivors of crimean-Congo hemorrhagic fever. Cell 184, 3486–3501 e3421.

    3. Freitas, N., Enguehard, M., Denolly, S., Levy, C., Neveu, G., Lerolle, S., Devignot, S., Weber, F., Bergeron, E., Legros, V., Cosset, F.L., 2020. The interplays between crimeanCongo hemorrhagic fever virus (cchfv) m segment-encoded accessory proteins and structural proteins promote virus assembly and infectivity. PLoS Pathog. 16, e1008850.

    4. Golden, J.W., Shoemaker, C.J., Lindquist, M.E., Zeng, X., Daye, S.P., Williams, J.A., Liu, J., Coffin, K.M., Olschner, S., Flusin, O., Altamura, L.A., Kuehl, K.A.,Fitzpatrick, C.J., Schmaljohn, C.S., Garrison, A.R., 2019. Gp38-targeting monoclonal antibodies protect adult mice against lethal crimean-Congo hemorrhagic fever virus infection. Sci. Adv. 5, eaaw9535.

    5. Hulswit, R.J.G., Paesen, G.C., Bowden, T.A., Shi, X.H., 2021. Recent advances in bunyavirus glycoprotein research: precursor processing, receptor binding and structure. Viruses-Basel 13, 353.

    6. Klein, D.E., Choi, J.L., Harrison, S.C., 2013. Structure of a dengue virus envelope protein late-stage fusion intermediate. J. Virol. 87, 2287–2293.

    7. Li, N., Rao, G., Li, Z., Yin, J., Chong, T., Tian, K., Fu, Y., Cao, S., 2022. Cryo-em structure of glycoprotein c from crimean-Congo hemorrhagic fever virus. Virol. Sin. 37, 127–213.

    8. Mishra, A.K., Hellert, J., Freitas, N., Guardado-Calvo, P., Haouz, A., Fels, J.M., Maurer, D.P., Abelson, D.M., Bornholdt, Z.A., Walker, L.M., Chandran, K., Cosset, F.L., McLellan, J.S., Rey, F.A., 2022. Structural basis of synergistic neutralization of crimean-Congo hemorrhagic fever virus by human antibodies. Science 375, 104–109.

    9. Mishra, A.K., Moyer, C.L., Abelson, D.M., Deer, D.J., El Omari, K., Duman, R., Lobel, L., Lutwama, J.J., Dye, J.M., Wagner, A., Chandran, K., Cross, R.W., Geisbert, T.W., Zeitlin, L., Bornholdt, Z.A., McLellan, J.S., 2020. Structure and characterization of crimean-Congo hemorrhagic fever virus gp38. J. Virol. 94, e02005–e02019.

    10. Modis, Y., Ogata, S., Clements, D., Harrison, S.C., 2003. A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc. Natl. Acad. Sci. U. S. A. 100, 6986–6991.

    11. Yang, X., Lee, J., Mahony, E.M., Kwong, P.D., Wyatt, R., Sodroski, J., 2002. Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of t4 bacteriophage fibritin. J. Virol. 76, 4634–4642.

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    The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed; many more still need an answer

      Corresponding author: Wei Ye, virologyyw@fmmu.edu.cn
      Corresponding author: Yingfeng Lei, yflei@fmmu.edu.cn
      Corresponding author: Fanglin Zhang, flzhang@fmmu.edu.cn
    • a Department of Microbiology, School of Preclinical Medicine, Airforce Medical University:Fourth Military Medical University, Xi'an, 710032, China;
    • b Department of Infectious Diseases, Tangdu Hospital, Airforce Medical University:Fourth Military Medical University, Xi'an, 710038, China;
    • c Department of Dermatology, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China

    Abstract: Highlights
    1. The structure of glycoprotein Gc, responsible for mediating membrane fusion between cell and CCHFV, is revealed, but many more mysteries remain.
    2. Why do only antibodies against Gc have neutralizing effect, but not the one against Gn?
    3. Why can NAbs against Gc only be protective in the animals in preventive settings, but not in the therapeutic administration?

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