Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody

Melissa Wirawan; Guntur Fibriansah; Jan K. Marzinek; Xin Xiang Lim; Thiam Seng Ng; Adelene Y.L. Sim; Qian Zhang; Victor A. Kostyuchenko; Jian Shi; Scott A. Smith; Chandra S. Verma; Ganesh Anand; James E. Crowe; Peter J. Bond; Shee Mei Lok

doi:10.1016/j.str.2018.10.009

Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody

Melissa Wirawan, Guntur Fibriansah, Jan K. Marzinek, Xin Xiang Lim, Thiam Seng Ng, Adelene Y.L. Sim, Qian Zhang, Victor A. Kostyuchenko, Jian Shi, Scott A. Smith, Chandra S. Verma, Ganesh Anand, James E. Crowe, Peter J. Bond, Shee Mei Lok

Chemistry

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	253-267.e8
Journal	Structure
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.str.2018.10.009
State	Published - Feb 5 2019

All Science Journal Classification (ASJC) codes

Structural Biology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.str.2018.10.009

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Wirawan, M., Fibriansah, G., Marzinek, J. K., Lim, X. X., Ng, T. S., Sim, A. Y. L., Zhang, Q., Kostyuchenko, V. A., Shi, J., Smith, S. A., Verma, C. S., Anand, G., Crowe, J. E., Bond, P. J., & Lok, S. M. (2019). Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody. Structure, 27(2), 253-267.e8. https://doi.org/10.1016/j.str.2018.10.009

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title = "Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody",

abstract = "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.",

author = "Melissa Wirawan and Guntur Fibriansah and Marzinek, {Jan K.} and Lim, {Xin Xiang} and Ng, {Thiam Seng} and Sim, {Adelene Y.L.} and Qian Zhang and Kostyuchenko, {Victor A.} and Jian Shi and Smith, {Scott A.} and Verma, {Chandra S.} and Ganesh Anand and Crowe, {James E.} and Bond, {Peter J.} and Lok, {Shee Mei}",

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doi = "10.1016/j.str.2018.10.009",

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T1 - Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody

AU - Wirawan, Melissa

AU - Fibriansah, Guntur

AU - Marzinek, Jan K.

AU - Lim, Xin Xiang

AU - Ng, Thiam Seng

AU - Sim, Adelene Y.L.

AU - Zhang, Qian

AU - Kostyuchenko, Victor A.

AU - Shi, Jian

AU - Smith, Scott A.

AU - Verma, Chandra S.

AU - Anand, Ganesh

AU - Crowe, James E.

AU - Bond, Peter J.

AU - Lok, Shee Mei

PY - 2019/2/5

Y1 - 2019/2/5

N2 - 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.

AB - 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.

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Mechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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