| http://purl.uniprot.org/citations/27531907 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27531907 | http://www.w3.org/2000/01/rdf-schema#comment | "UnlabelledHuman immunodeficiency virus type 1 (HIV-1) groups M, N, O, and P are the result of independent zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting great apes in Africa. Among these, only Vpu proteins of pandemic HIV-1 group M strains evolved potent activity against the restriction factor tetherin, which inhibits virus release from infected cells. Thus, effective Vpu-mediated tetherin antagonism may have been a prerequisite for the global spread of HIV-1. To determine whether this particular function enhances primary HIV-1 replication and interferon resistance, we introduced mutations into the vpu genes of HIV-1 group M and N strains to specifically disrupt their ability to antagonize tetherin, but not other Vpu functions, such as degradation of CD4, down-modulation of CD1d and NTB-A, and suppression of NF-κB activity. Lack of particular human-specific adaptations reduced the ability of HIV-1 group M Vpu proteins to enhance virus production and release from primary CD4(+) T cells at high levels of type I interferon (IFN) from about 5-fold to 2-fold. Interestingly, transmitted founder HIV-1 strains exhibited higher virion release capacity than chronic control HIV-1 strains irrespective of Vpu function, and group M viruses produced higher levels of cell-free virions than an N group HIV-1 strain. Thus, efficient virus release from infected cells seems to play an important role in the spread of HIV-1 in the human population and requires a fully functional Vpu protein that counteracts human tetherin.ImportanceUnderstanding which human-specific adaptations allowed HIV-1 to cause the AIDS pandemic is of great importance. One feature that distinguishes pandemic HIV-1 group M strains from nonpandemic or rare group O, N, and P viruses is the acquisition of mutations in the accessory Vpu protein that confer potent activity against human tetherin. Adaptation was required because human tetherin has a deletion that renders it resistant to the Nef protein used by the SIV precursor of HIV-1 to antagonize this antiviral factor. It has been suggested that these adaptations in Vpu were critical for the effective spread of HIV-1 M strains, but direct evidence has been lacking. Here, we show that these changes in Vpu significantly enhance virus replication and release in human CD4(+) T cells, particularly in the presence of IFN, thus supporting an important role in the spread of pandemic HIV-1."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.org/dc/terms/identifier | "doi:10.1128/mbio.00934-16"xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Hahn B.H."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Kirchhoff F."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Sauter D."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Iyer S.S."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Sturzel C.M."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/author | "Kmiec D."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/name | "mBio"xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/pages | "e00934-16"xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/title | "Vpu-Mediated Counteraction of Tetherin Is a Major Determinant of HIV-1 Interferon Resistance."xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/27531907 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27531907 |
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