Modest attenuation of HIV-1 Vpu alleles derived from elite controller plasma

PloS One
Jingyan ChenOliver T Fackler

Abstract

In the absence of antiretroviral therapy, infection with human immunodeficiency virus type 1 (HIV-1) can typically not be controlled by the infected host and results in the development of acquired immunodeficiency. In rare cases, however, patients spontaneously control HIV-1 replication. Mechanisms by which such elite controllers (ECs) achieve control of HIV-1 replication include particularly efficient immune responses as well as reduced fitness of the specific virus strains. To address whether polymorphisms in the accessory HIV-1 protein Vpu are associated with EC status we functionally analyzed a panel of plasma-derived vpu alleles from 15 EC and 16 chronic progressor (CP) patients. Antagonism of the HIV particle release restriction by the intrinsic immunity factor CD317/tetherin was well conserved among EC and CP Vpu alleles, underscoring the selective advantage of this Vpu function in HIV-1 infected individuals. In contrast, interference with CD317/tetherin induced NF-κB activation was little conserved in both groups. EC Vpus more frequently displayed reduced ability to downregulate cell surface levels of CD4 and MHC class I (MHC-I) molecules as well as of the NK cell ligand NTB-A. Polymorphisms potentially associated with ...Continue Reading

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Citations

Dec 15, 2015·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Johanna GalaskiOliver T Fackler
Aug 25, 2017·Future Microbiology·Megan E MayJoel N Blankson
May 14, 2016·Journal of Virology·François M PujolOliver T Fackler
Mar 8, 2019·Journal of Virology·Zachary A SilverRonald C Desrosiers
Jun 17, 2020·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Benedikt ObermaierOliver T Fackler

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Datasets Mentioned

BETA
EU517748
EU517730
EU517737
EU517745
EU517759
EU517754
EU517757
EU517723
KM656058
KM656073

Methods Mentioned

BETA
PCR
transfection
flow
flow cytometry
transfections
genotyping

Software Mentioned

Cyflogic
Clustal Omega
LSM5
GraphPad Prism
Adobe Photoshop
CellQuest Pro
BD
Zeiss

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