Matches in SemOpenAlex for { <https://semopenalex.org/work/W2965754771> ?p ?o ?g. }
- W2965754771 abstract "Human immunodeficiency virus type 1 (HIV-1) has evolved elaborate ways to evade immune cell recognition, including downregulation of classical HLA class I (HLA-I) from the surfaces of infected cells. Recent evidence identified HLA-E, a nonclassical HLA-I, as an important part of the antiviral immune response to HIV-1. Changes in HLA-E surface levels and peptide presentation can prompt both CD8+ T-cell and natural killer (NK) cell responses to viral infections. Previous studies reported unchanged or increased HLA-E levels on HIV-1-infected cells. Here, we examined HLA-E surface levels following infection of CD4+ T cells with primary HIV-1 strains and observed that a subset downregulated HLA-E. Two primary strains of HIV-1 that induced the strongest reduction in surface HLA-E expression were chosen for further testing. Expression of single Nef or Vpu proteins in a T-cell line, as well as tail swap experiments exchanging the cytoplasmic tail of HLA-A2 with that of HLA-E, demonstrated that Nef modulated HLA-E surface levels and targeted the cytoplasmic tail of HLA-E. Furthermore, infection of primary CD4+ T cells with HIV-1 mutants showed that a lack of functional Nef (and Vpu to some extent) impaired HLA-E downmodulation. Taken together, the results of this study demonstrate for the first time that HIV-1 can downregulate HLA-E surface levels on infected primary CD4+ T cells, potentially rendering them less vulnerable to CD8+ T-cell recognition but at increased risk of NKG2A+ NK cell killing.IMPORTANCE For almost two decades, it was thought that HIV-1 selectively downregulated the highly expressed HLA-I molecules HLA-A and HLA-B from the cell surface in order to evade cytotoxic-T-cell recognition, while leaving HLA-C and HLA-E molecules unaltered. It was stipulated that HIV-1 infection thereby maintained inhibition of NK cells via inhibitory receptors that bind HLA-C and HLA-E. This concept was recently revised when a study showed that primary HIV-1 strains reduce HLA-C surface levels, whereas the cell line-adapted HIV-1 strain NL4-3 lacks this ability. Here, we demonstrate that infection with distinct primary HIV-1 strains results in significant downregulation of surface HLA-E levels. Given the increasing evidence for HLA-E as an important modulator of CD8+ T-cell and NKG2A+ NK cell functions, this finding has substantial implications for future immunomodulatory approaches aimed at harnessing cytotoxic cellular immunity against HIV." @default.
- W2965754771 created "2019-08-13" @default.
- W2965754771 creator A5000112132 @default.
- W2965754771 creator A5000132836 @default.
- W2965754771 creator A5019198664 @default.
- W2965754771 creator A5023241639 @default.
- W2965754771 creator A5028344925 @default.
- W2965754771 creator A5041471505 @default.
- W2965754771 creator A5042817775 @default.
- W2965754771 creator A5044838008 @default.
- W2965754771 creator A5046049520 @default.
- W2965754771 creator A5046584692 @default.
- W2965754771 creator A5051677576 @default.
- W2965754771 creator A5059159168 @default.
- W2965754771 creator A5061287975 @default.
- W2965754771 creator A5066787287 @default.
- W2965754771 creator A5071551266 @default.
- W2965754771 creator A5075006919 @default.
- W2965754771 date "2019-10-15" @default.
- W2965754771 modified "2023-10-17" @default.
- W2965754771 title "Primary HIV-1 Strains Use Nef To Downmodulate HLA-E Surface Expression" @default.
- W2965754771 cites W138856452 @default.
- W2965754771 cites W14494190 @default.
- W2965754771 cites W1530787989 @default.
- W2965754771 cites W1574590275 @default.
- W2965754771 cites W1602245252 @default.
- W2965754771 cites W1659719610 @default.
- W2965754771 cites W1674854702 @default.
- W2965754771 cites W1804480117 @default.
- W2965754771 cites W1906987668 @default.
- W2965754771 cites W1976212425 @default.
- W2965754771 cites W1977282539 @default.
- W2965754771 cites W1980214977 @default.
- W2965754771 cites W1980662641 @default.
- W2965754771 cites W1980843873 @default.
- W2965754771 cites W1983262897 @default.
- W2965754771 cites W1989166597 @default.
- W2965754771 cites W1990126716 @default.
- W2965754771 cites W1990760248 @default.
- W2965754771 cites W1991982391 @default.
- W2965754771 cites W1994255893 @default.
- W2965754771 cites W1995513136 @default.
- W2965754771 cites W2003051762 @default.
- W2965754771 cites W2007089157 @default.
- W2965754771 cites W2007922771 @default.
- W2965754771 cites W2008923412 @default.
- W2965754771 cites W2015326137 @default.
- W2965754771 cites W2018966828 @default.
- W2965754771 cites W2023528999 @default.
- W2965754771 cites W2027999752 @default.
- W2965754771 cites W2030710089 @default.
- W2965754771 cites W2034207391 @default.
- W2965754771 cites W2040133121 @default.
- W2965754771 cites W2042309401 @default.
- W2965754771 cites W2042695720 @default.
- W2965754771 cites W2044569404 @default.
- W2965754771 cites W2045551237 @default.
- W2965754771 cites W2049461480 @default.
- W2965754771 cites W2057567758 @default.
- W2965754771 cites W2058321555 @default.
- W2965754771 cites W2058340238 @default.
- W2965754771 cites W2059801006 @default.
- W2965754771 cites W2066532177 @default.
- W2965754771 cites W2070214550 @default.
- W2965754771 cites W2073973240 @default.
- W2965754771 cites W2078837813 @default.
- W2965754771 cites W2080173792 @default.
- W2965754771 cites W2086462809 @default.
- W2965754771 cites W2088437777 @default.
- W2965754771 cites W2097168605 @default.
- W2965754771 cites W2100733882 @default.
- W2965754771 cites W2102820230 @default.
- W2965754771 cites W2104816728 @default.
- W2965754771 cites W2105021838 @default.
- W2965754771 cites W2107186721 @default.
- W2965754771 cites W2108912173 @default.
- W2965754771 cites W2109130469 @default.
- W2965754771 cites W2110065044 @default.
- W2965754771 cites W2110299975 @default.
- W2965754771 cites W2112336765 @default.
- W2965754771 cites W2117172344 @default.
- W2965754771 cites W2123584222 @default.
- W2965754771 cites W2126141460 @default.
- W2965754771 cites W2129780452 @default.
- W2965754771 cites W2134559961 @default.
- W2965754771 cites W2138637758 @default.
- W2965754771 cites W2152681964 @default.
- W2965754771 cites W2155068656 @default.
- W2965754771 cites W2157824753 @default.
- W2965754771 cites W2158099800 @default.
- W2965754771 cites W2161105060 @default.
- W2965754771 cites W2175125998 @default.
- W2965754771 cites W2178579396 @default.
- W2965754771 cites W2263787476 @default.
- W2965754771 cites W2266873158 @default.
- W2965754771 cites W2273220476 @default.
- W2965754771 cites W2284841043 @default.
- W2965754771 cites W2320400608 @default.
- W2965754771 cites W2339522572 @default.
- W2965754771 cites W2371536864 @default.