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 language | English |
|---|---|
| Article number | 16082 |
| Journal | Nature Microbiology |
| Volume | 1 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Jun 6 2016 |
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ASJC Scopus subject areas
- Microbiology
- Applied Microbiology and Biotechnology
- Immunology
- Microbiology (medical)
- Cell Biology
- Genetics
Cite this
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 journal › Article
}
TY - JOUR
T1 - Platelet-derived growth factor-α receptor is the cellular receptor for human cytomegalovirus gHgLgO trimer
AU - Kabanova, Anna
AU - Marcandalli, Jessica
AU - Zhou, Tongqing
AU - Bianchi, Siro
AU - Baxa, Ulrich
AU - Tsybovsky, Yaroslav
AU - Lilleri, Daniele
AU - Silacci-Fregni, Chiara
AU - Foglierini, Mathilde
AU - Fernandez-Rodriguez, Blanca Maria
AU - Druz, Aliaksandr
AU - Zhang, Baoshan
AU - Geiger, Roger
AU - Pagani, Massimiliano
AU - Sallusto, Federica
AU - Kwong, Peter D.
AU - Corti, Davide
AU - Lanzavecchia, Antonio
AU - Perez, Laurent
PY - 2016/6/6
Y1 - 2016/6/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991256812&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991256812&partnerID=8YFLogxK
U2 - 10.1038/nmicrobiol.2016.82
DO - 10.1038/nmicrobiol.2016.82
M3 - Article
AN - SCOPUS:84991256812
VL - 1
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 8
M1 - 16082
ER -