The role of cytomegalovirus gH/gL glycoprotein complexes in infection

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Human cytomegalovirus (HCMV) infections are a major cause of morbidity and mortality in immunocompromised hosts. Though anti-HCMV therapies exist, the rapid development of resistance calls for new, complementing strategies. Common targets for antiviral therapy are for example envelope glycoproteins which promote virus entry. Herpesvirus gH/gL glycoprotein complexes are essential for fusion of the viral envelope with a cellular membrane in the process of virus entry. The core gH/gL dimer is complemented with additional proteins which can bind to specific receptors and/or may guide the virus particles through specific exit pathways. For HCMV, two alternative gH/gL complexes have been identified, which in vitro define tropism and influence virus release, yet, whose function in the human infection is not clarified. The aims of this project are to identify the cellular receptor through which HCMV gH/gL complexes define tropism for certain cell types and to identify the homologous gH/gL complexes of the murine cytomegalovirus (MCMV). Then the role of these complexes will be studied in vivo in the mouse model using deletion mutants of MCMV gH/gL complexes.