Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody

Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can un...

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Main Authors: Wirawan, Melissa, Fibriansah, Guntur, Marzinek, Jan K., Lim, Xin Xiang, Ng, Thiam-Seng, Sim, Adelene Y. L., Zhang, Qian, Kostyuchenko, Victor A., Shi, Jian, Smith, Scott A., Verma, Chandra Shekhar, Anand, Ganesh, Crowe, James E., Bond, Peter J., Lok, Shee-Mei
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/146757
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1467572023-02-28T17:08:06Z Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody Wirawan, Melissa Fibriansah, Guntur Marzinek, Jan K. Lim, Xin Xiang Ng, Thiam-Seng Sim, Adelene Y. L. Zhang, Qian Kostyuchenko, Victor A. Shi, Jian Smith, Scott A. Verma, Chandra Shekhar Anand, Ganesh Crowe, James E. Bond, Peter J. Lok, Shee-Mei School of Biological Sciences Bioinformatics Institute, A*STAR Science::Biological sciences Cryo-EM Dengue Virus Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop. Here, we determined cryoelectron microscopy (cryo-EM) maps of the immDENV:anti-prM complex at different pH values, mimicking the extracellular (pH 8.0) or endosomal (pH 5.0) environments. At pH 5.0, there are two structural classes with fewer antibodies bound than at pH 8.0. These classes may represent different maturation states. Molecular simulations, together with the measured high-affinity pr:antibody interaction (versus the weak pr:E interaction) and also the low pH cryo-EM structures, suggest how antibody:pr complex can dislodge from the E protein at low pH. This exposes the E protein fusion loop enhancing virus interaction with endosomes. Ministry of Education (MOE) National Research Foundation (NRF) Accepted version This study has been supported by the following grants awarded to S.-M.L., National Research Foundation Singapore Investigatorship (NRF-NRFI2016-01); to J.E.C., United States National Institutes of Health grant U54 AI057157 (the Region IV Southeast Regional Center of Excellence in Emerging Infections and Biodefense); and to S.A.S., United States National Institutes of Health grant K08 AI103038. S.-M.L., P.J.B., C.S.V., and G.A. thank Ministry of Education, Singapore, (MOE2012-T3-008) for support. 2021-03-09T08:51:56Z 2021-03-09T08:51:56Z 2018 Journal Article Wirawan, M., Fibriansah, G., Marzinek, J. K., Lim, X. X., Ng, T.-S., Sim, A. Y. L., . . . Lok, S-M. (2019). Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody. Structure, 27(2), 253-267. doi:10.1016/j.str.2018.10.009 0969-2126 https://hdl.handle.net/10356/146757 10.1016/j.str.2018.10.009 30471923 2 27 253 267 en Structure © 2018 Elsevier Ltd. All rights reserved. This paper was published in Structure and is made available with permission of Elsevier Ltd. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Cryo-EM
Dengue Virus
spellingShingle Science::Biological sciences
Cryo-EM
Dengue Virus
Wirawan, Melissa
Fibriansah, Guntur
Marzinek, Jan K.
Lim, Xin Xiang
Ng, Thiam-Seng
Sim, Adelene Y. L.
Zhang, Qian
Kostyuchenko, Victor A.
Shi, Jian
Smith, Scott A.
Verma, Chandra Shekhar
Anand, Ganesh
Crowe, James E.
Bond, Peter J.
Lok, Shee-Mei
Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
description Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop. Here, we determined cryoelectron microscopy (cryo-EM) maps of the immDENV:anti-prM complex at different pH values, mimicking the extracellular (pH 8.0) or endosomal (pH 5.0) environments. At pH 5.0, there are two structural classes with fewer antibodies bound than at pH 8.0. These classes may represent different maturation states. Molecular simulations, together with the measured high-affinity pr:antibody interaction (versus the weak pr:E interaction) and also the low pH cryo-EM structures, suggest how antibody:pr complex can dislodge from the E protein at low pH. This exposes the E protein fusion loop enhancing virus interaction with endosomes.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Wirawan, Melissa
Fibriansah, Guntur
Marzinek, Jan K.
Lim, Xin Xiang
Ng, Thiam-Seng
Sim, Adelene Y. L.
Zhang, Qian
Kostyuchenko, Victor A.
Shi, Jian
Smith, Scott A.
Verma, Chandra Shekhar
Anand, Ganesh
Crowe, James E.
Bond, Peter J.
Lok, Shee-Mei
format Article
author Wirawan, Melissa
Fibriansah, Guntur
Marzinek, Jan K.
Lim, Xin Xiang
Ng, Thiam-Seng
Sim, Adelene Y. L.
Zhang, Qian
Kostyuchenko, Victor A.
Shi, Jian
Smith, Scott A.
Verma, Chandra Shekhar
Anand, Ganesh
Crowe, James E.
Bond, Peter J.
Lok, Shee-Mei
author_sort Wirawan, Melissa
title Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
title_short Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
title_full Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
title_fullStr Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
title_full_unstemmed Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody
title_sort mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prm antibody
publishDate 2021
url https://hdl.handle.net/10356/146757
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