Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/28331088http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28331088http://www.w3.org/2000/01/rdf-schema#comment"Antibodies recognizing conserved CD4-induced (CD4i) epitopes on human immunodeficiency virus type 1 (HIV-1) Env and able to mediate antibody-dependent cellular cytotoxicity (ADCC) have been shown to be present in sera from most HIV-1-infected individuals. These antibodies preferentially recognize Env in its CD4-bound conformation. CD4 downregulation by Nef and Vpu dramatically reduces exposure of CD4i HIV-1 Env epitopes and therefore reduce the susceptibility of HIV-1-infected cells to ADCC mediated by HIV-positive (HIV+) sera. Importantly, this mechanism of immune evasion can be circumvented with small-molecule CD4 mimetics (CD4mc) that are able to transition Env into the CD4-bound conformation and sensitize HIV-1-infected cells to ADCC mediated by HIV+ sera. However, HIV-1 developed additional mechanisms to avoid ADCC, including Vpu-mediated BST-2 antagonism, which decreases the overall amount of Env present at the cell surface. Accordingly, BST-2 upregulation in response to alpha interferon (IFN-α) was shown to increase the susceptibility of HIV-1-infected cells to ADCC despite the activity of Vpu. Here we show that BST-2 upregulation by IFN-β and interleukin-27 (IL-27) also increases the surface expression of Env and thus boosts the ability of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from HIV-1-infected individuals.IMPORTANCE HIV-1 evolved sophisticated strategies to conceal Env epitopes from ADCC-mediating antibodies present in HIV+ sera. Vpu-mediated BST-2 downregulation was shown to decrease ADCC responses by limiting the amount of Env present at the cell surface. This effect of Vpu was shown to be attenuated by IFN-α treatment. Here we show that in addition to IFN-α, IFN-β and IL-27 also affect Vpu-mediated BST-2 downregulation and greatly enhance ADCC responses against HIV-1-infected cells in the presence of CD4mc. These findings may inform strategies aimed at HIV prevention and eradication."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.org/dc/terms/identifier"doi:10.1128/jvi.00219-17"xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Hahn B.H."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Ding S."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Evans D.T."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Kirchhoff F."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Sauter D."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Sodroski J."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Bibollet-Ruche F."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Melillo B."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Gee K."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Kaufmann D.E."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Finzi A."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Neil S.J."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Smith A.B."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Richard J."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Medjahed H."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Prevost J."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Coutu M."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"Brassard N."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/author"von Bredow B."xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/name"J Virol"xsd:string
http://purl.uniprot.org/citations/28331088http://purl.uniprot.org/core/pages"e00219-17"xsd:string
▶