Abstract:
:Herpes simplex virus (HSV) is an important human pathogen with a high worldwide seroprevalence. HSV enters epithelial cells, the primary site of infection, by a low-pH pathway. HSV glycoprotein B (gB) undergoes low pH-induced conformational changes, which are thought to drive membrane fusion. When neutralized back to physiological pH, these changes become reversible. Here, HSV-infected cells were subjected to short pulses of radiolabeling, followed by immunoprecipitation with a panel of gB monoclonal antibodies (MAbs), demonstrating that gB folds and oligomerizes rapidly and cotranslationally in the endoplasmic reticulum. Full-length gB from transfected cells underwent low-pH-triggered changes in oligomeric conformation in the absence of other viral proteins. MAbs to gB neutralized HSV entry into cells regardless of the pH dependence of the entry pathway, suggesting a conservation of gB function in distinct fusion mechanisms. The combination of heat and acidic pH triggered irreversible changes in the antigenic conformation of the gB fusion domain, while changes in the gB oligomer remained reversible. An elevated temperature alone was not sufficient to induce gB conformational change. Together, these results shed light on the conformation and function of the HSV-1 gB oligomer, which serves as part of the core fusion machinery during viral entry.IMPORTANCE Herpes simplex virus (HSV) causes infection of the mouth, skin, eyes, and genitals and establishes lifelong latency in humans. gB is conserved among all herpesviruses. HSV gB undergoes reversible conformational changes following exposure to acidic pH which are thought to mediate fusion and entry into epithelial cells. Here, we identified cotranslational folding and oligomerization of newly synthesized gB. A panel of antibodies to gB blocked both low-pH and pH-neutral entry of HSV, suggesting conserved conformational changes in gB regardless of cell entry route. Changes in HSV gB conformation were not triggered by increased temperature alone, in contrast to results with EBV gB. Acid pH-induced changes in the oligomeric conformation of gB are related but distinct from pH-triggered changes in gB antigenic conformation. These results highlight critical aspects of the class III fusion protein, gB, and inform strategies to block HSV infection at the level of fusion and entry.
journal_name
J Viroljournal_title
Journal of virologyauthors
Weed DJ,Dollery SJ,Komala Sari T,Nicola AVdoi
10.1128/JVI.01034-18subject
Has Abstractpub_date
2018-08-16 00:00:00issue
17eissn
0022-538Xissn
1098-5514pii
JVI.01034-18journal_volume
92pub_type
杂志文章abstract::We have examined the attachment and penetration phenotypes of several glycoprotein gIII mutants of pseudorabies virus (PRV) and have identified the first one-third of gIII as a region that mediates efficient virus attachment to PK15 and Vero cells. This portion of gIII, amino acids 25 through 157 of the wild-type sequ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2646-2654.1993
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.2.1196-1199.1994
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.6.2059-2066.1988
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pub_type: 杂志文章
doi:10.1128/JVI.72.9.7598-7602.1998
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pub_type: 杂志文章
doi:10.1128/JVI.69.12.8102-8108.1995
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doi:10.1128/JVI.00230-11
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.3.962-964.1980
更新日期:1980-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.24.2.651-661.1977
更新日期:1977-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.10.8393-8402.1999
更新日期:1999-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.2.709-716.1976
更新日期:1976-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00631-20
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.6.1164-1167.1967
更新日期:1967-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.3.1343-1350.2005
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.14.1.133-138.1974
更新日期:1974-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.25.1.349-360.1978
更新日期:1978-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02203-14
更新日期:2014-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2009-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.46.1.131-136.1983
更新日期:1983-04-01 00:00:00
abstract::The four major Epstein-Barr virion envelope components were separated by column chromatography and reconstituted into artificial liposomes. These liposomes were tested for their ability to bind selectively to Epstein-Barr virus receptor-positive cells. Only when the two high-molecular-weight glycoproteins, VE1 and VE2...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.41.1.286-297.1982
更新日期:1982-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00571-15
更新日期:2015-07-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4947-4951.2001
更新日期:2001-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00537-07
更新日期:2007-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.536-541.1986
更新日期:1986-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02040-14
更新日期:2014-12-01 00:00:00