Structure of the hepatitis C virus E1E2 glycoprotein complex

Alba Torrents de la Peña; Kwinten Sliepen; Lisa Eshun-Wilson; Maddy L. Newby; Joel D. Allen; Ian Zon; Sylvie Koekkoek; Ana Chumbe; Max Crispin; Janke Schinkel; Gabriel C. Lander; Rogier W. Sanders; Andrew B. Ward

doi:https://doi.org/10.1126/science.abn9884

Structure of the hepatitis C virus E1E2 glycoprotein complex

Alba Torrents de la Peña, Kwinten Sliepen, Lisa Eshun-Wilson, Maddy L. Newby, Joel D. Allen, Ian Zon, Sylvie Koekkoek, Ana Chumbe, Max Crispin, Janke Schinkel, Gabriel C. Lander, Rogier W. Sanders, Andrew B. Ward

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

23 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.

Original language	English
Pages (from-to)	263-269
Number of pages	7
Journal	Science
Volume	378
Issue number	6617
DOIs	https://doi.org/10.1126/science.abn9884
Publication status	Published - 21 Oct 2022

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title = "Structure of the hepatitis C virus E1E2 glycoprotein complex",

abstract = "Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.",

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AU - Torrents de la Peña, Alba

AU - Sliepen, Kwinten

AU - Eshun-Wilson, Lisa

AU - Newby, Maddy L.

AU - Allen, Joel D.

AU - Zon, Ian

AU - Koekkoek, Sylvie

AU - Chumbe, Ana

AU - Crispin, Max

AU - Schinkel, Janke

AU - Lander, Gabriel C.

AU - Sanders, Rogier W.

AU - Ward, Andrew B.

PY - 2022/10/21

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AB - Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma in humans and afflicts more than 58 million people worldwide. The HCV envelope E1 and E2 glycoproteins are essential for viral entry and comprise the primary antigenic target for neutralizing antibody responses. The molecular mechanisms of E1E2 assembly, as well as how the E1E2 heterodimer binds broadly neutralizing antibodies, remain elusive. Here, we present the cryo-electron microscopy structure of the membrane-extracted full-length E1E2 heterodimer in complex with three broadly neutralizing antibodies-AR4A, AT1209, and IGH505-at ~3.5-angstrom resolution. We resolve the interface between the E1 and E2 ectodomains and deliver a blueprint for the rational design of vaccine immunogens and antiviral drugs.

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JO - Science

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Structure of the hepatitis C virus E1E2 glycoprotein complex

Abstract

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