{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T04:51:55Z","timestamp":1773204715501,"version":"3.50.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI097274"],"award-info":[{"award-number":["R01AI097274"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The tropism of human cytomegalovirus (HCMV) is influenced by the envelope glycoprotein complexes gH\/gL\/gO and gH\/gL\/UL128-131. During virion assembly, gO and the UL128-131 proteins compete for binding to gH\/gL in the endoplasmic reticulum (ER). This assembly process clearly differs among strains, since Merlin (ME) virions contain abundant gH\/gL\/UL128-131 and little gH\/gL\/gO, whereas TR contains much higher levels of total gH\/gL, mostly in the form of gH\/gL\/gO, but much lower levels of gH\/gL\/UL128-131 than ME. Remaining questions include (i) what are the mechanisms behind these assembly differences, and (ii) do differences reflect\n                    <jats:italic>in vitro<\/jats:italic>\n                    culture adaptations or natural genetic variations? Since the UL74(gO) open reading frame (ORF) differs in 25% of amino acids between TR and ME, we analyzed recombinant viruses in which the UL74(gO) ORF was swapped. TR virions were &gt;40-fold more infectious than ME. Transcriptional repression of UL128-131 enhanced the infectivity of ME to the level of TR, despite still far lower levels of gH\/gL\/gO. Swapping the UL74(gO) ORF had no effect on either TR or ME. A quantitative immunoprecipitation approach revealed that gH\/gL expression levels were within 4-fold between TR and ME, but the gO expression level was 20-fold lower for ME, which suggested differences in mRNA transcription, translation, or rapid ER-associated degradation of gO.\n                    <jats:italic>trans<\/jats:italic>\n                    -Complementation of gO expression during ME replication gave a 6-fold enhancement of infectivity beyond the 40-fold effect of UL128-131 repression alone. Overall, strain variations in the assembly of gH\/gL complexes result from differences in the expression of gO and UL128-131, and selective advantages for reduced UL128-131 expression during fibroblast propagation are much stronger than those for higher gO expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Specific genetic differences between independently isolated HCMV strains may result from purifying selection on\n                    <jats:italic>de novo<\/jats:italic>\n                    mutations arising during propagation in culture or random sampling among the diversity of genotypes present in clinical specimens. Results presented indicate that while reduced UL128-131 expression may confer a powerful selective advantage during cell-free propagation of HCMV in fibroblast cultures, selective pressures for increased gO expression are much weaker. Thus, variation in gO expression among independent strains may represent natural genotype variability present\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This may have important implications for virus-host interactions, such as immune recognition, and underscores the value of studying molecular mechanisms of replication using multiple HCMV strains.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00606-18","type":"journal-article","created":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T05:34:42Z","timestamp":1525930482000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Expression Levels of Glycoprotein O (gO) Vary between Strains of Human Cytomegalovirus, Influencing the Assembly of gH\/gL Complexes and Virion Infectivity"],"prefix":"10.1128","volume":"92","author":[{"given":"Le","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Biological Sciences, 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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Stanton","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom"},{"name":"MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-7656","authenticated-orcid":false,"given":"Jeremy","family":"Kamil","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA"},{"name":"Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.01.059"},{"key":"e_1_3_2_3_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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