{"id":{"repo_id":"gmu","oai_identifier":"oai:MARS:1920/14556"},"canonical_url":"https://search.dev.ndltd.org/etd/gmu/oai:MARS:1920/14556","repository":{"repo_id":"gmu","name":"George Mason University","base_url":"https://mars.gmu.edu/server/oai/request"},"display":{"title":"MOLECULAR CHARACTERIZATION OF PSGL-1 DECAMERIC REPEATS FOR INACTIVATING HIV-1 INFECTIVITY","abstract":"P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is a dimeric glycoprotein that has been identified as a restriction enzyme factor of HIV-1. PSGL-1 is expressed on the surface of CD4+ T cells, primarily on lymphoid and myeloid cells. This mucin-like surface protein binds to P, E, and L selectin, is upregulated during inflammation, and mediates leukocyte tethering and rolling. Previous studies showed PSGL-1 blocks the infectivity of virions released through steric hindrance, preventing particles from attaching to target cells. Mapping studies showed PSGL-1’s extracellular N-terminus is needed for the antiviral activity. Polymorphisms of PSGL-1 contain an extracellular domain containing 14-16 tandem repeats of 10 amino acids, with the consensus sequence, (-A-T/M-E-A-Q-T-T-X-P/L-A/T-). The extracellular region contains highly O-glycosylated Threonines (30%) and Prolines (10%), which in addition to the tandem repeats form a sturdy elongated backbone for the protein. To determine if the presence of the decameric repeats (DRs) in PSGL-1 is required for its anti-HIV activity, we performed DR deletion mutagenesis studies of PSGL-1, deleting single DR to all DRs. We found that deleting all DRs eliminated PSGL-1’s antiviral activity, but the presence of a single DR, dependent on location, was sufficient to maintain its antiviral activity. The PSGL-1 mutant containing 1 DR has lower antiviral activity than full-length PSGL-1. Mutagenesis of N-linked and O-linked glycosylation sites inside and outside the DRs demonstrated that these sites contribute to PSGL-1’s restriction of HIV-1 activity. However, residues involved in selectin-binding did not appear to be critical for PSGL-1’s antiviral activity. Furthermore, we show that the availability of glucose also affected the antiviral activity of PSGL-1. The results demonstrate that PSGL-1 maintains significant antiviral activity in the absence of certain decameric repeats and the presence of glycosylation sites also influences its anti-HIV activity.","abstract_html":"P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is a dimeric glycoprotein that has been identified as a restriction enzyme factor of HIV-1. PSGL-1 is expressed on the surface of CD4+ T cells, primarily on lymphoid and myeloid cells. This mucin-like surface protein binds to P, E, and L selectin, is upregulated during inflammation, and mediates leukocyte tethering and rolling. Previous studies showed PSGL-1 blocks the infectivity of virions released through steric hindrance, preventing particles from attaching to target cells. Mapping studies showed PSGL-1’s extracellular N-terminus is needed for the antiviral activity. Polymorphisms of PSGL-1 contain an extracellular domain containing 14-16 tandem repeats of 10 amino acids, with the consensus sequence, (-A-T/M-E-A-Q-T-T-X-P/L-A/T-). The extracellular region contains highly O-glycosylated Threonines (30%) and Prolines (10%), which in addition to the tandem repeats form a sturdy elongated backbone for the protein. To determine if the presence of the decameric repeats (DRs) in PSGL-1 is required for its anti-HIV activity, we performed DR deletion mutagenesis studies of PSGL-1, deleting single DR to all DRs. We found that deleting all DRs eliminated PSGL-1’s antiviral activity, but the presence of a single DR, dependent on location, was sufficient to maintain its antiviral activity. The PSGL-1 mutant containing 1 DR has lower antiviral activity than full-length PSGL-1. Mutagenesis of N-linked and O-linked glycosylation sites inside and outside the DRs demonstrated that these sites contribute to PSGL-1’s restriction of HIV-1 activity. However, residues involved in selectin-binding did not appear to be critical for PSGL-1’s antiviral activity. Furthermore, we show that the availability of glucose also affected the antiviral activity of PSGL-1. The results demonstrate that PSGL-1 maintains significant antiviral activity in the absence of certain decameric repeats and the presence of glycosylation sites also influences its anti-HIV activity.","abstract_has_math":false,"creators":["Sealey, Leanna"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-27T19:51:46Z","subjects":["Anti-viral","Glycosylation","HIV-1","P-selectin Glycoprotein Ligand 1","PSGL-1","Restriction factor"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/14556"],"render_values":[{"text":"hdl:1920/14556","href":null,"code":true}]}]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2023"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Anti-viral","Glycosylation","HIV-1","P-selectin Glycoprotein Ligand 1","PSGL-1","Restriction factor"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["hdl:1920/14556"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.other","label":"Dc Description Other","values":["P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is a dimeric glycoprotein that has been identified as a restriction enzyme factor of HIV-1. PSGL-1 is expressed on the surface of CD4+ T cells, primarily on lymphoid and myeloid cells. This mucin-like surface protein binds to P, E, and L selectin, is upregulated during inflammation, and mediates leukocyte tethering and rolling. Previous studies showed PSGL-1 blocks the infectivity of virions released through steric hindrance, preventing particles from attaching to target cells. Mapping studies showed PSGL-1’s extracellular N-terminus is needed for the antiviral activity. Polymorphisms of PSGL-1 contain an extracellular domain containing 14-16 tandem repeats of 10 amino acids, with the consensus sequence, (-A-T/M-E-A-Q-T-T-X-P/L-A/T-). The extracellular region contains highly O-glycosylated Threonines (30%) and Prolines (10%), which in addition to the tandem repeats form a sturdy elongated backbone for the protein. To determine if the presence of the decameric repeats (DRs) in PSGL-1 is required for its anti-HIV activity, we performed DR deletion mutagenesis studies of PSGL-1, deleting single DR to all DRs. We found that deleting all DRs eliminated PSGL-1’s antiviral activity, but the presence of a single DR, dependent on location, was sufficient to maintain its antiviral activity. The PSGL-1 mutant containing 1 DR has lower antiviral activity than full-length PSGL-1. Mutagenesis of N-linked and O-linked glycosylation sites inside and outside the DRs demonstrated that these sites contribute to PSGL-1’s restriction of HIV-1 activity. However, residues involved in selectin-binding did not appear to be critical for PSGL-1’s antiviral activity. Furthermore, we show that the availability of glucose also affected the antiviral activity of PSGL-1. The results demonstrate that PSGL-1 maintains significant antiviral activity in the absence of certain decameric repeats and the presence of glycosylation sites also influences its anti-HIV activity."]},{"key":"dc:title","label":"Title","values":["MOLECULAR CHARACTERIZATION OF PSGL-1 DECAMERIC REPEATS FOR INACTIVATING HIV-1 INFECTIVITY"]}]}],"canonical_facts":{"dc:date.issued":["2023"],"dc:description.other":["P-selectin glycoprotein ligand-1 (PSGL-1/CD162) is a dimeric glycoprotein that has been identified as a restriction enzyme factor of HIV-1. PSGL-1 is expressed on the surface of CD4+ T cells, primarily on lymphoid and myeloid cells. This mucin-like surface protein binds to P, E, and L selectin, is upregulated during inflammation, and mediates leukocyte tethering and rolling. Previous studies showed PSGL-1 blocks the infectivity of virions released through steric hindrance, preventing particles from attaching to target cells. Mapping studies showed PSGL-1’s extracellular N-terminus is needed for the antiviral activity. Polymorphisms of PSGL-1 contain an extracellular domain containing 14-16 tandem repeats of 10 amino acids, with the consensus sequence, (-A-T/M-E-A-Q-T-T-X-P/L-A/T-). The extracellular region contains highly O-glycosylated Threonines (30%) and Prolines (10%), which in addition to the tandem repeats form a sturdy elongated backbone for the protein. To determine if the presence of the decameric repeats (DRs) in PSGL-1 is required for its anti-HIV activity, we performed DR deletion mutagenesis studies of PSGL-1, deleting single DR to all DRs. We found that deleting all DRs eliminated PSGL-1’s antiviral activity, but the presence of a single DR, dependent on location, was sufficient to maintain its antiviral activity. The PSGL-1 mutant containing 1 DR has lower antiviral activity than full-length PSGL-1. Mutagenesis of N-linked and O-linked glycosylation sites inside and outside the DRs demonstrated that these sites contribute to PSGL-1’s restriction of HIV-1 activity. However, residues involved in selectin-binding did not appear to be critical for PSGL-1’s antiviral activity. Furthermore, we show that the availability of glucose also affected the antiviral activity of PSGL-1. The results demonstrate that PSGL-1 maintains significant antiviral activity in the absence of certain decameric repeats and the presence of glycosylation sites also influences its anti-HIV activity."],"dc:identifier":["hdl:1920/14556"],"dc:subject":["Anti-viral","Glycosylation","HIV-1","P-selectin Glycoprotein Ligand 1","PSGL-1","Restriction factor"],"dc:title":["MOLECULAR CHARACTERIZATION OF PSGL-1 DECAMERIC REPEATS FOR INACTIVATING HIV-1 INFECTIVITY"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T19:51:46Z"}