HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex

Laetitia Zona; Joachim Lupberger; Nazha Sidahmed-Adrar; Christine Thumann; Helen J Harris; Amy Barnes; Jonathan Florentin; Rajiv G Tawar; Fei Xiao; Marine Turek; Sarah C Durand; François H T Duong; Markus H Heim; François-Loïc Cosset; Ivan Hirsch; Didier Samuel; Laurent Brino; Mirjam B Zeisel; François Le Naour; Jane A McKeating; Thomas F Baumert

doi:10.1016/j.chom.2013.02.006

HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex

Laetitia Zona, Joachim Lupberger, Nazha Sidahmed-Adrar, Christine Thumann, Helen J Harris, Amy Barnes, Jonathan Florentin, Rajiv G Tawar, Fei Xiao, Marine Turek, Sarah C Durand, François H T Duong, Markus H Heim, François-Loïc Cosset, Ivan Hirsch, Didier Samuel, Laurent Brino, Mirjam B Zeisel, François Le Naour, Jane A McKeatingThomas F Baumert

Immunology and Immunotherapy

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

114 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) entry is dependent on coreceptor complex formation between the tetraspanin superfamily member CD81 and the tight junction protein claudin-1 (CLDN1) on the host cell membrane. The receptor tyrosine kinase EGFR acts as a cofactor for HCV entry by promoting CD81-CLDN1 complex formation via unknown mechanisms. We identify the GTPase HRas, activated downstream of EGFR signaling, as a key host signal transducer for EGFR-mediated HCV entry. Proteomic analysis revealed that HRas associates with tetraspanin CD81, CLDN1, and the previously unrecognized HCV entry cofactors integrin β1 and Ras-related protein Rap2B in hepatocyte membranes. HRas signaling is required for lateral membrane diffusion of CD81, which enables tetraspanin receptor complex assembly. HRas was also found to be relevant for entry of other viruses, including influenza. Our data demonstrate that viruses exploit HRas signaling for cellular entry by compartmentalization of entry factors and receptor trafficking.

Original language	English
Pages (from-to)	302-13
Number of pages	12
Journal	Cell Host & Microbe
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2013.02.006
Publication status	Published - 13 Mar 2013

Keywords

Antigens, CD81
Claudin-1
Hepacivirus
Hepatitis C
Humans
Protein Binding
Protein Multimerization
Proto-Oncogene Proteins p21(ras)
Receptor, Epidermal Growth Factor
Signal Transduction
Tetraspanins
Virus Internalization

UN SDGs

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

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10.1016/j.chom.2013.02.006

The Role of Hepatitis C Virus Glycoprotein-Receptor Polymorphism in Viral Pathogenesis
McKeating, J. (Principal Investigator)
Medical Research Council
1/01/12 → 30/06/17
Project: Research Councils
MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)
Jenkinson, E. (Principal Investigator)
Medical Research Council
3/08/09 → 30/09/17
Project: Research Councils

Cite this

Zona, L., Lupberger, J., Sidahmed-Adrar, N., Thumann, C., Harris, H. J., Barnes, A., Florentin, J., Tawar, R. G., Xiao, F., Turek, M., Durand, S. C., Duong, F. H. T., Heim, M. H., Cosset, F.-L., Hirsch, I., Samuel, D., Brino, L., Zeisel, M. B., Le Naour, F., ... Baumert, T. F. (2013). HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex. Cell Host & Microbe, 13(3), 302-13. https://doi.org/10.1016/j.chom.2013.02.006

@article{43eba266a1484d4e88ab8e8493caa621,

title = "HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex",

abstract = "Hepatitis C virus (HCV) entry is dependent on coreceptor complex formation between the tetraspanin superfamily member CD81 and the tight junction protein claudin-1 (CLDN1) on the host cell membrane. The receptor tyrosine kinase EGFR acts as a cofactor for HCV entry by promoting CD81-CLDN1 complex formation via unknown mechanisms. We identify the GTPase HRas, activated downstream of EGFR signaling, as a key host signal transducer for EGFR-mediated HCV entry. Proteomic analysis revealed that HRas associates with tetraspanin CD81, CLDN1, and the previously unrecognized HCV entry cofactors integrin β1 and Ras-related protein Rap2B in hepatocyte membranes. HRas signaling is required for lateral membrane diffusion of CD81, which enables tetraspanin receptor complex assembly. HRas was also found to be relevant for entry of other viruses, including influenza. Our data demonstrate that viruses exploit HRas signaling for cellular entry by compartmentalization of entry factors and receptor trafficking.",

keywords = "Antigens, CD81, Claudin-1, Hepacivirus, Hepatitis C, Humans, Protein Binding, Protein Multimerization, Proto-Oncogene Proteins p21(ras), Receptor, Epidermal Growth Factor, Signal Transduction, Tetraspanins, Virus Internalization",

author = "Laetitia Zona and Joachim Lupberger and Nazha Sidahmed-Adrar and Christine Thumann and Harris, {Helen J} and Amy Barnes and Jonathan Florentin and Tawar, {Rajiv G} and Fei Xiao and Marine Turek and Durand, {Sarah C} and Duong, {Fran{\c c}ois H T} and Heim, {Markus H} and Fran{\c c}ois-Lo{\"i}c Cosset and Ivan Hirsch and Didier Samuel and Laurent Brino and Zeisel, {Mirjam B} and {Le Naour}, Fran{\c c}ois and McKeating, {Jane A} and Baumert, {Thomas F}",

year = "2013",

month = mar,

day = "13",

doi = "10.1016/j.chom.2013.02.006",

language = "English",

volume = "13",

pages = "302--13",

journal = "Cell Host & Microbe",

issn = "1931-3128",

publisher = "Elsevier",

number = "3",

}

Zona, L, Lupberger, J, Sidahmed-Adrar, N, Thumann, C, Harris, HJ, Barnes, A, Florentin, J, Tawar, RG, Xiao, F, Turek, M, Durand, SC, Duong, FHT, Heim, MH, Cosset, F-L, Hirsch, I, Samuel, D, Brino, L, Zeisel, MB, Le Naour, F, McKeating, JA & Baumert, TF 2013, 'HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex', Cell Host & Microbe, vol. 13, no. 3, pp. 302-13. https://doi.org/10.1016/j.chom.2013.02.006

TY - JOUR

T1 - HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex

AU - Zona, Laetitia

AU - Lupberger, Joachim

AU - Sidahmed-Adrar, Nazha

AU - Thumann, Christine

AU - Harris, Helen J

AU - Barnes, Amy

AU - Florentin, Jonathan

AU - Tawar, Rajiv G

AU - Xiao, Fei

AU - Turek, Marine

AU - Durand, Sarah C

AU - Duong, François H T

AU - Heim, Markus H

AU - Cosset, François-Loïc

AU - Hirsch, Ivan

AU - Samuel, Didier

AU - Brino, Laurent

AU - Zeisel, Mirjam B

AU - Le Naour, François

AU - McKeating, Jane A

AU - Baumert, Thomas F

PY - 2013/3/13

Y1 - 2013/3/13

N2 - Hepatitis C virus (HCV) entry is dependent on coreceptor complex formation between the tetraspanin superfamily member CD81 and the tight junction protein claudin-1 (CLDN1) on the host cell membrane. The receptor tyrosine kinase EGFR acts as a cofactor for HCV entry by promoting CD81-CLDN1 complex formation via unknown mechanisms. We identify the GTPase HRas, activated downstream of EGFR signaling, as a key host signal transducer for EGFR-mediated HCV entry. Proteomic analysis revealed that HRas associates with tetraspanin CD81, CLDN1, and the previously unrecognized HCV entry cofactors integrin β1 and Ras-related protein Rap2B in hepatocyte membranes. HRas signaling is required for lateral membrane diffusion of CD81, which enables tetraspanin receptor complex assembly. HRas was also found to be relevant for entry of other viruses, including influenza. Our data demonstrate that viruses exploit HRas signaling for cellular entry by compartmentalization of entry factors and receptor trafficking.

AB - Hepatitis C virus (HCV) entry is dependent on coreceptor complex formation between the tetraspanin superfamily member CD81 and the tight junction protein claudin-1 (CLDN1) on the host cell membrane. The receptor tyrosine kinase EGFR acts as a cofactor for HCV entry by promoting CD81-CLDN1 complex formation via unknown mechanisms. We identify the GTPase HRas, activated downstream of EGFR signaling, as a key host signal transducer for EGFR-mediated HCV entry. Proteomic analysis revealed that HRas associates with tetraspanin CD81, CLDN1, and the previously unrecognized HCV entry cofactors integrin β1 and Ras-related protein Rap2B in hepatocyte membranes. HRas signaling is required for lateral membrane diffusion of CD81, which enables tetraspanin receptor complex assembly. HRas was also found to be relevant for entry of other viruses, including influenza. Our data demonstrate that viruses exploit HRas signaling for cellular entry by compartmentalization of entry factors and receptor trafficking.

KW - Antigens, CD81

KW - Claudin-1

KW - Hepacivirus

KW - Hepatitis C

KW - Humans

KW - Protein Binding

KW - Protein Multimerization

KW - Proto-Oncogene Proteins p21(ras)

KW - Receptor, Epidermal Growth Factor

KW - Signal Transduction

KW - Tetraspanins

KW - Virus Internalization

U2 - 10.1016/j.chom.2013.02.006

DO - 10.1016/j.chom.2013.02.006

M3 - Article

C2 - 23498955

SN - 1931-3128

VL - 13

SP - 302

EP - 313

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 3

ER -

HRas signal transduction promotes hepatitis C virus cell entry by triggering assembly of the host tetraspanin receptor complex

Abstract

Keywords

UN SDGs

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Projects

The Role of Hepatitis C Virus Glycoprotein-Receptor Polymorphism in Viral Pathogenesis

MRC Centre For Immune Regulation (Linked to DCDF.RRAK10540) (Linked to 14810 & 14835)

Cite this