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

• Verfasst von: Chen, Jingyan [VerfasserIn]
• Verfasst von: Tibroni, Nadine [VerfasserIn]
• Verfasst von: Galaski, Johanna [VerfasserIn]
• Verfasst von: Müller, Birthe [VerfasserIn]
• Verfasst von: Haller, Claudia [VerfasserIn]
• Verfasst von: Fackler, Oliver Till [VerfasserIn]
• Titel: Modest attenuation of HIV-1 Vpu alleles derived from elite controller plasma
• Verf.angabe: Jingyan Chen, Nadine Tibroni, Daniel Sauter, Johanna Galaski, Toshiyuki Miura, Galit Alter, Birthe Mueller, Claudia Haller, Bruce D. Walker, Frank Kirchhoff, Zabrina L. Brumme, Takamasa Ueno, Oliver T. Fackler
• Fussnoten: Gesehen am 23.08.2017
• Titel Quelle: Enthalten in: Public Library of Science: PLoS one
• Jahr Quelle: 2015
• Band/Heft Quelle: 10(2015,3) Artikel-Nummer e0120434, 19 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0120434
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1562655787

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-κBactivation 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 high affinity interactions of the inhibitory killer immunoglobulin-like receptor (KIR) KIR2DL2 were significantly enriched among EC Vpus but did not account for these functional differences. Together these results suggest that in a subgroup of EC patients, some Vpu functions are modestly reduced, possibly as a result of host selection.