This project is aimed towards a more complete understanding of the assembly of envelope glycoprotein complexes of human cytomegalovirus (HCMV) that mediate attachment and entry into different types of cells in the body. HCMV is a ubiquitous pathogen that causes a wide range of severe diseases in individuals with undeveloped or compromised immune systems. Therapies are limited, and candidate vaccines have failed to elicit protective immunity. Recent advances have contributed to the view that the attachment/entry-mediating glycoproteins encoded by HCMV include those that provide ?universal? functions for entry into all cell types, and those that provide ?niche-specific? functions for entry into specific cell types. Infection of all cells by herpes viruses requires fusion mediated by the fusion glycoprotein, gB, and the cofactor gH/gL. For HCMV, gH/gL can be bound by either gO, or UL128-131. The gH/gL/gO complex appears to mediate gB fusion, whereas the gH/gL/UL128-131 complex facilitates infection of select cell types though a poorly characterized, non-fusion mechanism. The goals of the proposed project are to: 1) distinguish the functions and mechanism of the gH/gL complexes by analyzing a library of gH/gL mutants 2) analyze the cell type specific neutralizing activity of anti-gH antibodies 3) evaluate a panel human epithelial cells derived from different tissues as host cells for HCMV replication. replication.
Human cytomegalovirus (HCMV) causes a wide range of severe disease states in newborns, and adults with compromised immune systems. Therapies and vaccines have been limited by an incomplete understanding of how the virus attaches to and infects the different types of cells in the body. This project studies the surface molecules of HCMV that mediate cell-type dependent infection mechanisms.
| Zhang, Le; Zhou, Momei; Stanton, Richard et al. (2018) Expression Levels of Glycoprotein O (gO) Vary between Strains of Human Cytomegalovirus, Influencing the Assembly of gH/gL Complexes and Virion Infectivity. J Virol 92: |
| Schultz, Eric P; Lanchy, Jean-Marc; Ellerbeck, Erin E et al. (2016) Scanning Mutagenesis of Human Cytomegalovirus Glycoprotein gH/gL. J Virol 90:2294-305 |
| Zhou, Momei; Lanchy, Jean-Marc; Ryckman, Brent J (2015) Human Cytomegalovirus gH/gL/gO Promotes the Fusion Step of Entry into All Cell Types, whereas gH/gL/UL128-131 Broadens Virus Tropism through a Distinct Mechanism. J Virol 89:8999-9009 |
| Zhou, Momei; Yu, Qin; Wechsler, Anya et al. (2013) Comparative analysis of gO isoforms reveals that strains of human cytomegalovirus differ in the ratio of gH/gL/gO and gH/gL/UL128-131 in the virion envelope. J Virol 87:9680-90 |
