Relative Resistance of HLA-B to Downregulation by Naturally Occurring HIV-1 Nef Sequences

MBio
Macdonald MahitiTakamasa Ueno

Abstract

HIV-1 Nef binds to the cytoplasmic region of HLA-A and HLA-B and downregulates these molecules from the surface of virus-infected cells, thus evading immune detection by CD8(+) T cells. Polymorphic residues within the HLA cytoplasmic region may affect Nef's downregulation activity. However, the effects of HLA polymorphisms on recognition by primary Nef isolates remain elusive, as do the specific Nef regions responsible for downregulation of HLA-A versus HLA-B. Here, we examined 46 Nef clones isolated from chronically HIV-1 subtype B-infected subjects for their ability to downregulate various HLA-A, HLA-B, and HLA-C molecules on the surface of virus-infected cells. Overall, HLA-B exhibited greater resistance to Nef-mediated downregulation than HLA-A, regardless of the cell type examined. As expected, no Nef clone downregulated HLA-C. Importantly, the differential abilities of patient-derived Nef clones to downregulate HLA-A and HLA-B correlated inversely with the sensitivities of HIV-infected target cells to recognition by effector cells expressing an HIV-1 Gag-specific T cell receptor. Nef codon function analysis implicated amino acid variation at position 202 (Nef-202) in differentially affecting the ability to downregulate HL...Continue Reading

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Citations

Jan 17, 2020·Journal of Medical Virology·Jaclyn K MannThumbi Ndung'u
Nov 8, 2019·American Journal of Respiratory Cell and Molecular Biology·Marco Pio La MannaNadia Caccamo
Aug 4, 2019·Journal of Virology·Thomas van Stigt ThansAngelique Hölzemer
Jan 13, 2018·Journal of Virology·Zachary EndeEric Hunter
Aug 9, 2019·Virus Evolution·John P BartonThumbi Ndung'u

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Datasets Mentioned

BETA
JX440926
JX440971

Methods Mentioned

BETA
flow cytometry
PCR
genotyping

Software Mentioned

Graph Pad Prism

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