Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer
Articolo
Data di Pubblicazione:
2016
Citazione:
Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer / A. Kabanova, J. Marcandalli, T. Zhou, S. Bianchi, U. Baxa, Y. Tsybovsky, D. Lilleri, C. Silacci Fregni, M. Foglierini, B.M. Fernandez Rodriguez, A. Druz, B. Zhang, R. Geiger, M. Pagani, F. Sallusto, P.D. Kwong, D. Corti, A. Lanzavecchia, L. Perez. - In: NATURE MICROBIOLOGY. - ISSN 2058-5276. - 1:8(2016 Jun). [10.1038/nmicrobiol.2016.82]
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
microbiology; applied microbiology and biotechnology; immunology; microbiology (medical); cell biology; genetics
Elenco autori:
A. Kabanova, J. Marcandalli, T. Zhou, S. Bianchi, U. Baxa, Y. Tsybovsky, D. Lilleri, C. Silacci Fregni, M. Foglierini, B.M. Fernandez Rodriguez, A. Druz, B. Zhang, R. Geiger, M. Pagani, F. Sallusto, P.D. Kwong, D. Corti, A. Lanzavecchia, L. Perez
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