Nadia S El-Hamdi1, K Yeon Choi1, Alistair McGregor2. 1. Dept. Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX, USA. 2. Dept. Microbial Pathogenesis & Immunology, College of Medicine, Texas A&M University, Bryan, TX, USA. Electronic address: mcgalistair2013@tamu.edu.
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.
Species-specific guinea pig cytomegalovirus (pan class="Species">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 humanPDGFRAexpression did not complement GPCMV(PC-)infection, a potential basis for viral species specificity.
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