{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:49:49Z","timestamp":1789940989295,"version":"4.0.1"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Interaction between gH\/gL and the fusion protein gB is likely a conserved feature of the entry mechanism for all herpesviruses. Human cytomegalovirus (HCMV) gH\/gL can be bound by gO or by the set of proteins UL128, UL130, and UL131, forming gH\/gL\/gO and gH\/gL\/UL128-131. The mechanisms by which these complexes facilitate entry are poorly understood. Mutants lacking UL128-131 replicate well on fibroblasts but fail to enter epithelial\/endothelial cells, and this has led to the general assumption that gH\/gL\/UL128-131 promotes gB-mediated fusion on epithelial\/endothelial cells whereas gH\/gL\/gO provides this function on fibroblasts. This was challenged by observations that gO-null mutants were defective on all of these cell types, suggesting that entry into epithelial\/endothelial cells requires both of the gH\/gL complexes, but the severe replication defect of the gO mutants precluded detailed analysis. We previously reported that the ratio of gH\/gL\/gO and gH\/gL\/UL128-131 in the virion envelope varied dramatically among HCMV strains. Here, we show that strains not only differ in the ratio, but also vary in the total amount of gH\/gL in the virion. Cell-type-specific particle-to-PFU ratios of HCMV strains that contained different amounts of gH\/gL\/gO and gH\/gL\/UL128-131 were determined. Infection of both fibroblasts and epithelial cells was generally correlated with the abundance of gH\/gL\/gO, but not with that of gH\/gL\/UL128-131. The low infectivity of virions rich in gH\/gL\/UL128-131 but low in gH\/gL\/gO could be overcome by treatment with the chemical fusogen polyethylene glycol (PEG), strongly arguing that gH\/gL\/gO provides the conserved herpesvirus gH\/gL entry function of promoting gB-mediated fusion for entry into all cell types, whereas gH\/gL\/UL128-131 acts through a distinct mechanism to allow infection of select cell types.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    The functions of HCMV gH\/gL complexes in entry are unclear. Unlike the well-studied Epstein-Barr virus (EBV), where gH\/gL and gH\/gL\/gp42 complexes both seem capable of promoting gB fusion during entry into different cell types, our studies here suggest that for HCMV, gH\/gL\/gO promotes gB fusion on all cell types, whereas gH\/gL\/UL128-131 broadens virus tropism through a distinct, as yet unknown mechanism. To our knowledge, this is the first suggestion of a herpesvirus gH\/gL that does not act by promoting gB fusion, which might make HCMV a useful model to study the fundamental mechanisms by which herpesvirus gH\/gL regulates gB fusion. Moreover, gH\/gL\/UL128-131 is a candidate vaccine target. Our findings help to explain the cell-type-dependent virus neutralization exhibited by anti-gH\/gL\/UL128-131 antibodies and underscore the importance of gH\/gL\/gO as another important part of vaccine or therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1128\/jvi.01325-15","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T22:46:26Z","timestamp":1434581186000},"page":"8999-9009","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":177,"title":["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"],"prefix":"10.1128","volume":"89","author":[{"given":"Momei","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, Montana, USA"},{"name":"Cellular, Molecular and Microbial Biology Program, University of Montana, Missoula, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Lanchy","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, Montana, USA"},{"name":"Cellular, Molecular and Microbial Biology Program, University of Montana, Missoula, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brent J.","family":"Ryckman","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of Montana, Missoula, Montana, USA"},{"name":"Cellular, Molecular and Microbial Biology Program, University of Montana, Missoula, Montana, USA"},{"name":"Biochemistry and Biophysics Program, University of Montana, Missoula, Montana, USA"},{"name":"Center for Biomolecular Structure and Dynamics, University of Montana, Missoula, Montana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"417","article-title":"Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease","volume":"325","author":"Britt WJ","year":"2008","unstructured":"Britt WJ. 2008. 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