Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer

Anna Kabanova, Jessica Marcandalli, Tongqing Zhou, Siro Bianchi, Ulrich Baxa, Yaroslav Tsybovsky, Daniele Lilleri, Chiara Silacci-Fregni, Mathilde Foglierini, Blanca Maria Fernandez-Rodriguez, Aliaksandr Druz, Baoshan Zhang, Roger Geiger, Massimiliano Pagani, Federica Sallusto, Peter D. Kwong, Davide Corti, Antonio Lanzavecchia, Laurent Perez

Research output: Contribution to journalArticle

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Abstract

Human cytomegalovirus encodes at least 25 membrane glycoproteins that are found in the viral envelope1. While gB represents the fusion protein, two glycoprotein complexes control the tropism of the virus: the gHgLgO trimer is involved in the infection of fibroblasts, and the gHgLpUL128L pentamer is required for infection of endothelial, epithelial and myeloid cells 2-5. Two reports suggested that gB binds to ErbB1 and PDGFRα (refs 6,7); however, these results do not explain the tropism of the virus and were recently challenged 8,9. Here, we provide a 19â €...Å reconstruction for the gHgLgO trimer and show that it binds with high affinity through the gO subunit to PDGFRα, which is expressed on fibroblasts but not on epithelial cells. We also provide evidence that the trimer is essential for viral entry in both fibroblasts and epithelial cells. Furthermore, we identify the pentamer, which is essential for infection of epithelial cells, as a trigger for the ErbB pathway. These findings help explain the broad tropism of human cytomegalovirus and indicate that PDGFRα and the viral gO subunit could be targeted by novel anti-viral therapies.

Original languageEnglish
Article number16082
JournalNature Microbiology
Volume1
Issue number8
DOIs
Publication statusPublished - Jun 6 2016

Fingerprint

Platelet-Derived Growth Factor Receptors
Tropism
Epithelial Cells
Fibroblasts
Cytomegalovirus
Infection
Viruses
Membrane Glycoproteins
Myeloid Cells
Glycoproteins
Endothelial Cells
cytomegalovirus receptor
Proteins
Therapeutics

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology
  • Immunology
  • Microbiology (medical)
  • Cell Biology
  • Genetics

Cite this

Kabanova, A., Marcandalli, J., Zhou, T., Bianchi, S., Baxa, U., Tsybovsky, Y., ... Perez, L. (2016). Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. Nature Microbiology, 1(8), [16082]. https://doi.org/10.1038/nmicrobiol.2016.82

Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. / Kabanova, Anna; Marcandalli, Jessica; Zhou, Tongqing; Bianchi, Siro; Baxa, Ulrich; Tsybovsky, Yaroslav; Lilleri, Daniele; Silacci-Fregni, Chiara; Foglierini, Mathilde; Fernandez-Rodriguez, Blanca Maria; Druz, Aliaksandr; Zhang, Baoshan; Geiger, Roger; Pagani, Massimiliano; Sallusto, Federica; Kwong, Peter D.; Corti, Davide; Lanzavecchia, Antonio; Perez, Laurent.

In: Nature Microbiology, Vol. 1, No. 8, 16082, 06.06.2016.

Research output: Contribution to journalArticle

Kabanova, A, Marcandalli, J, Zhou, T, Bianchi, S, Baxa, U, Tsybovsky, Y, Lilleri, D, Silacci-Fregni, C, Foglierini, M, Fernandez-Rodriguez, BM, Druz, A, Zhang, B, Geiger, R, Pagani, M, Sallusto, F, Kwong, PD, Corti, D, Lanzavecchia, A & Perez, L 2016, 'Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer', Nature Microbiology, vol. 1, no. 8, 16082. https://doi.org/10.1038/nmicrobiol.2016.82
Kabanova, Anna ; Marcandalli, Jessica ; Zhou, Tongqing ; Bianchi, Siro ; Baxa, Ulrich ; Tsybovsky, Yaroslav ; Lilleri, Daniele ; Silacci-Fregni, Chiara ; Foglierini, Mathilde ; Fernandez-Rodriguez, Blanca Maria ; Druz, Aliaksandr ; Zhang, Baoshan ; Geiger, Roger ; Pagani, Massimiliano ; Sallusto, Federica ; Kwong, Peter D. ; Corti, Davide ; Lanzavecchia, Antonio ; Perez, Laurent. / Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer. In: Nature Microbiology. 2016 ; Vol. 1, No. 8.
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