FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2155619102> ?p ?o ?g. }

• W2155619102 abstract "Abstract Background A nef gene is present in all primate lentiviral genomes and is important for high viral loads and progression to AIDS in human or experimental macaque hosts of HIV or SIV, respectively. In these hosts, infection of the thymus results in a decreased output of naive T cells that may contribute to the development of immunodeficiency. We have previously shown that HIV-1 subtype B Nef proteins can block human T-cell development. However, the underlying mechanism(s) and the conservation of this Nef function between different groups of HIV and SIV remained to be determined. Results We investigated whether reduction of thymic output is a conserved function of highly divergent lentiviral Nef proteins including those from both types of human immunodeficiency viruses (HIV-1 and HIV-2), their direct simian counterparts (SIVcpz, SIVgor and SIVsmm, respectively), and some additional SIV strains. We found that expression of most of these nef alleles in thymocyte progenitors impaired T-cell development and reduced thymic output. For HIV-1 Nef, binding to active p21 protein (Cdc42/Rac)-activated kinase (PAK2) was a major determinant of this function. In contrast, selective disruption of PAK2 binding did not eliminate the effect on T-cell development of SIVmac239 Nef, as was shown by expressing mutants in a newly discovered PAK2 activating structural motif (PASM) constituted by residues I117, H121, T218 and Y221, as well as previously described mutants. Rather, down-modulation of cell surface CD3 was sufficient for reduced thymic output by SIVmac Nef, while other functions of SIV Nefs contributed. Conclusions Our results indicate that primate lentiviral Nef proteins impair development of thymocyte precursors into T cells in multiple ways. The interaction of HIV-1 Nef with active PAK2 by HIV-1 seem to be most detrimental, and downregulation of CD3 by HIV-2 and most SIV Nef proteins sufficient for reduced thymic output. Since the reduction of thymic output by Nef is a conserved property of divergent lentiviruses, it is likely to be relevant for peripheral T-cell depletion in poorly adapted primate lentiviral infections." @default.
• W2155619102 created "2016-06-24" @default.
• W2155619102 creator A5000479325 @default.
• W2155619102 creator A5002032002 @default.
• W2155619102 creator A5003656228 @default.
• W2155619102 creator A5004304926 @default.
• W2155619102 creator A5011493742 @default.
• W2155619102 creator A5012583970 @default.
• W2155619102 creator A5020673989 @default.
• W2155619102 creator A5027339300 @default.
• W2155619102 creator A5035476712 @default.
• W2155619102 creator A5036034929 @default.
• W2155619102 creator A5045466674 @default.
• W2155619102 creator A5063657587 @default.
• W2155619102 creator A5068537765 @default.
• W2155619102 creator A5075006919 @default.
• W2155619102 creator A5075528637 @default.
• W2155619102 creator A5082745742 @default.
• W2155619102 creator A5087131663 @default.
• W2155619102 date "2013-11-15" @default.
• W2155619102 modified "2023-10-01" @default.
• W2155619102 title "Primate lentiviral Nef proteins deregulate T-cell development by multiple mechanisms" @default.
• W2155619102 cites W1033069450 @default.
• W2155619102 cites W1529197890 @default.
• W2155619102 cites W1580217007 @default.
• W2155619102 cites W1587913223 @default.
• W2155619102 cites W1892811633 @default.
• W2155619102 cites W1965938141 @default.
• W2155619102 cites W1983274903 @default.
• W2155619102 cites W1986512844 @default.
• W2155619102 cites W2004112238 @default.
• W2155619102 cites W2016723478 @default.
• W2155619102 cites W2017589058 @default.
• W2155619102 cites W2018306895 @default.
• W2155619102 cites W2019237006 @default.
• W2155619102 cites W2023650184 @default.
• W2155619102 cites W2025028670 @default.
• W2155619102 cites W2027844128 @default.
• W2155619102 cites W2043946604 @default.
• W2155619102 cites W2051931389 @default.
• W2155619102 cites W2053486179 @default.
• W2155619102 cites W2054362021 @default.
• W2155619102 cites W2054395379 @default.
• W2155619102 cites W2056429839 @default.
• W2155619102 cites W2063465748 @default.
• W2155619102 cites W2064557078 @default.
• W2155619102 cites W2066210679 @default.
• W2155619102 cites W2070278092 @default.
• W2155619102 cites W2072321096 @default.
• W2155619102 cites W2083492553 @default.
• W2155619102 cites W2083907420 @default.
• W2155619102 cites W2089794315 @default.
• W2155619102 cites W2090860161 @default.
• W2155619102 cites W2096071832 @default.
• W2155619102 cites W2102484003 @default.
• W2155619102 cites W2124122758 @default.
• W2155619102 cites W2127930176 @default.
• W2155619102 cites W2129104112 @default.
• W2155619102 cites W2131711570 @default.
• W2155619102 cites W2132634936 @default.
• W2155619102 cites W2135810929 @default.
• W2155619102 cites W2136784346 @default.
• W2155619102 cites W2136920402 @default.
• W2155619102 cites W2143900459 @default.
• W2155619102 cites W2145000176 @default.
• W2155619102 cites W2146998119 @default.
• W2155619102 cites W2147582981 @default.
• W2155619102 cites W2148750451 @default.
• W2155619102 cites W2151143752 @default.
• W2155619102 cites W2157701259 @default.
• W2155619102 cites W2158099800 @default.
• W2155619102 cites W2159897712 @default.
• W2155619102 cites W2160146754 @default.
• W2155619102 cites W2160519413 @default.
• W2155619102 cites W2162776293 @default.
• W2155619102 cites W2342220526 @default.
• W2155619102 cites W4236769279 @default.
• W2155619102 cites W87675469 @default.
• W2155619102 doi "https://doi.org/10.1186/1742-4690-10-137" @default.
• W2155619102 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3906981" @default.
• W2155619102 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24237970" @default.
• W2155619102 hasPublicationYear "2013" @default.
• W2155619102 type Work @default.
• W2155619102 sameAs 2155619102 @default.
• W2155619102 citedByCount "4" @default.
• W2155619102 countsByYear W21556191022015 @default.
• W2155619102 countsByYear W21556191022016 @default.
• W2155619102 countsByYear W21556191022020 @default.
• W2155619102 crossrefType "journal-article" @default.
• W2155619102 hasAuthorship W2155619102A5000479325 @default.
• W2155619102 hasAuthorship W2155619102A5002032002 @default.
• W2155619102 hasAuthorship W2155619102A5003656228 @default.
• W2155619102 hasAuthorship W2155619102A5004304926 @default.
• W2155619102 hasAuthorship W2155619102A5011493742 @default.
• W2155619102 hasAuthorship W2155619102A5012583970 @default.
• W2155619102 hasAuthorship W2155619102A5020673989 @default.
• W2155619102 hasAuthorship W2155619102A5027339300 @default.
• W2155619102 hasAuthorship W2155619102A5035476712 @default.
• W2155619102 hasAuthorship W2155619102A5036034929 @default.
• W2155619102 hasAuthorship W2155619102A5045466674 @default.

• next