TY - JOUR
T1 - Antibody-induced uncoating of human rhinovirus B14
AU - Dong, Yangchao
AU - Liu, Yue
AU - Jiang, Wen
AU - Smith, Thomas J.
AU - Xu, Zhikai
AU - Rossmann, Michael G.
N1 - Publisher Copyright:
© 2017, National Academy of Sciences. All rights reserved.
PY - 2017/7/25
Y1 - 2017/7/25
N2 - Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody–virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.
AB - Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody–virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.
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U2 - 10.1073/pnas.1707369114
DO - 10.1073/pnas.1707369114
M3 - Article
C2 - 28696310
AN - SCOPUS:85025681485
SN - 0027-8424
VL - 114
SP - 8017
EP - 8022
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 30
ER -