Wei Ye, Chuantao Ye, Yongliang Hu, Yangchao Dong, Yingfeng Lei and 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. doi: 10.1016/j.virs.2022.05.003
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 .VIROLOGICA SINICA, 2022, 37(4) : 634-636.  http://dx.doi.org/10.1016/j.virs.2022.05.003

克里米亚-刚果出血热病毒Gc糖蛋白结构终被解析,但更多疑问尚待回答

  • 中国拥有最丰富的猪流感病毒(SIV)生态系统,自2009年甲型H1N1流感大流行病毒(pdm/09)传入猪体内以来,大大增加了pdm/09与我国猪群中主要的流行的SIV——欧亚类禽型H1N1(EA H1N1)亚型SIV之间的重组频率。本研究在对我国山东地区的SIV流行病学监测中,从一个养猪场采集的样品中分离到一株高致病性的重组EA H1N1亚型SIV。通过对分离到的毒株进行8个片段全基因组测序以及系统发育分析,结果表明分离到的重组SIV包含两个来自EA H1N1谱系的表面基因和一个完整的来源于pdm/09的内部基因盒。进一步的小鼠致病性实验结果表明,分离到的重组SIV可以在不经过适应的情况下就能够在小鼠的肺脏内高效复制,并且对小鼠的致死率可达到100%,另外,病理切片的H&E染色结果显示该重组SIV能够引起小鼠肺脏组织严重的病理变化。目前许多国家都有关于人类感染EA H1N1亚型SIV的报道,因此,应该加强对猪群中重组EA H1N1亚型SIV的监测。

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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