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Guinea pig cytomegalovirus trimer complex gH/gL/gO uses PDGFRA as universal receptor for cell fusion and entry.
- Source :
-
Virology [Virology] 2020 Sep; Vol. 548, pp. 236-249. Date of Electronic Publication: 2020 Jun 11. - Publication Year :
- 2020
-
Abstract
- Species-specific guinea pig cytomegalovirus (GPCMV) causes congenital CMV and the virus encodes homolog glycoprotein complexes to human CMV, including gH-based trimer (gH/gL/gO) and pentamer-complex (PC). Platelet-derived growth factor receptor alpha (gpPDGFRA), only present on fibroblast cells, was identified via CRISPR as the putative receptor for PC-independent GPCMV infection. Immunoprecipitation assays demonstrated direct interaction of gH/gL/gO with gpPDGFRA but not in absence of gO. Expression of viral gB also resulted in precipitation of gB/gH/gL/gO/gpPDGFRA complex. Cell-cell fusion assays determined that expression of gpPDGFRA and gH/gL/gO in adjacent cells enabled cell fusion, which was not enhanced by gB. N-linked gpPDGFRA glycosylation inhibition had limited effect and blocking tyrosine kinase (TK) transduction had no impact on infection. Ectopically expressed gpPDGFRA or TK-domain mutant in trophoblast or epithelial cells previously non-susceptible to GPCMV(PC-) enabled viral infection. In contrast, transient human PDGFRA expression did not complement GPCMV(PC-) infection, a potential basis for viral species specificity.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Betaherpesvirinae genetics
Cell Fusion
Guinea Pigs
Herpesviridae Infections genetics
Herpesviridae Infections metabolism
Protein Binding
Receptor, Platelet-Derived Growth Factor alpha genetics
Rodent Diseases genetics
Rodent Diseases virology
Viral Proteins chemistry
Viral Proteins genetics
Virus Internalization
Betaherpesvirinae physiology
Herpesviridae Infections veterinary
Receptor, Platelet-Derived Growth Factor alpha metabolism
Rodent Diseases metabolism
Viral Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0341
- Volume :
- 548
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 32791352
- Full Text :
- https://doi.org/10.1016/j.virol.2020.05.012