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Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA
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Viruses 2018, 10(12), 704; https://doi.org/10.3390/v10120704
Received: 14 November 2018 / Revised: 4 December 2018 / Accepted: 5 December 2018 / Published: 11 December 2018
(This article belongs to the Special Issue Recent Advances in Cytomegalovirus Research)
The past few years have brought substantial progress toward understanding how human cytomegalovirus (HCMV) enters the remarkably wide spectrum of cell types and tissues that it infects. Neuropilin-2 and platelet-derived growth factor receptor alpha (PDGFRα) were identified as receptors, respectively, for the trimeric and pentameric glycoprotein H/glycoprotein L (gH/gL) complexes that in large part govern HCMV cell tropism, while CD90 and CD147 were also found to play roles during entry. X-ray crystal structures for the proximal viral fusogen, glycoprotein B (gB), and for the pentameric gH/gL complex (pentamer) have been solved. A novel virion gH complex consisting of gH bound to UL116 instead of gL was described, and findings supporting the existence of a stable complex between gH/gL and gB were reported. Additional work indicates that the pentamer promotes a mode of cell-associated spread that resists antibody neutralization, as opposed to the trimeric gH/gL complex (trimer), which appears to be broadly required for the infectivity of cell-free virions. Finally, viral factors such as UL148 and US16 were identified that can influence the incorporation of the alternative gH/gL complexes into virions. We will review these advances and their implications for understanding HCMV entry and cell tropism. View Full-Text
Keywords: viral entry; glycoproteins; receptors; cytomegalovirus; herpesviruses; HCMV; CMV; pentamer; trimer; gH/gL viral entry; glycoproteins; receptors; cytomegalovirus; herpesviruses; HCMV; CMV; pentamer; trimer; gH/gL
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Nguyen, C.C.; Kamil, J.P. Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism. Viruses 2018, 10, 704.

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