{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1175"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1175","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Identification and characterization of low pH-triggered conformational changes in the herpes simplex virus glycoprotein B","abstract":"Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.","abstract_html":"Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis.","abstract_has_math":false,"creators":["Dollery, Stephen"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Microbiology & Immunology","degree_department":null,"school":null,"contributors":["Anthony Nicola"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-03-02T08:00:00Z","date_published":"2011-03-02T08:00:00Z","updated_at":"2026-07-24T05:53:26Z","subjects":["herpes","simplex","glycoprotein","gB","virus entry","low pH","conformation","endocytosis","fusion","membrane fusion","s-gB","gB730","HSV","HSV-1","Medicine and Health Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/176"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/176","href":"https://scholarscompass.vcu.edu/etd/176","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/N926-WH48","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Anthony Nicola"]},{"key":"dc:creator","label":"Author","values":["Dollery, Stephen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2016-04-25T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology & Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["herpes","simplex","glycoprotein","gB","virus entry","low pH","conformation","endocytosis","fusion","membrane fusion","s-gB","gB730","HSV","HSV-1","Medicine and Health Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/N926-WH48","https://scholarscompass.vcu.edu/etd/176"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis."]},{"key":"dc:title","label":"Title","values":["Identification and characterization of low pH-triggered conformational changes in the herpes simplex virus glycoprotein B"]}]}],"canonical_facts":{"dc:contributor":["Anthony Nicola"],"dc:creator":["Dollery, Stephen"],"dc:date.available":["2016-04-25T07:00:00Z"],"dc:description.abstract":["Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to 6.0. The antigenic structure of gB functional region I that is critical for fusion is specifically altered by mildly acidic pH both in vitro and during entry into host cells. Point mutations within gB functional region 1 that block membrane fusion still allow conformational changes in region 1. This suggests that specific hydrophobic residues are essential for fusion domain insertion into the host cell membrane but not conformational change. The detected conformational changes were reversible, similar to other class III fusion glycoproteins. Exposure to mildly acidic pH directly triggered the fusion function of HSV glycoproteins and caused gB, but not other glycoproteins, to become more hydrophobic. The oligomeric conformation of gB is altered at a similar pH range. In addition, several approaches were used to monitor gB throughout glycoprotein synthesis and maturation. It is shown that gB may cotranslationally fold and oligomerize as it is synthesized on the ribosome. As gB matures it then alters conformation and/or binding partner to form antigenically distinct populations of gB within the cell and virion. I conclude that intracellular low pH induces changes in gB conformation that, together with additional triggers such as receptor-binding, are essential for virion-cell fusion during herpesviral entry by endocytosis."],"dc:identifier":["https://doi.org/10.25772/N926-WH48","https://scholarscompass.vcu.edu/etd/176"],"dc:rights":["© The Author"],"dc:subject":["herpes","simplex","glycoprotein","gB","virus entry","low pH","conformation","endocytosis","fusion","membrane fusion","s-gB","gB730","HSV","HSV-1","Medicine and Health Sciences"],"dc:title":["Identification and characterization of low pH-triggered conformational changes in the herpes simplex virus glycoprotein B"],"thesis:degree_discipline":["Microbiology & Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:53:26Z"}