Chen, JingyanTibroni, NadineSauter, DanielGalaski, JohannaMiura, ToshiyukiAlter, GalitMueller, BirtheHaller, ClaudiaWalker, BruceKirchhoff, FrankBrumme, Zabrina L.Ueno, TakamasaFackler, Oliver T.2015-04-012015Chen, J., N. Tibroni, D. Sauter, J. Galaski, T. Miura, G. Alter, B. Mueller, et al. 2015. “Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma.” PLoS ONE 10 (3): e0120434. doi:10.1371/journal.pone.0120434. http://dx.doi.org/10.1371/journal.pone.0120434.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351106In 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 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.en-USJournal Article2015-04-0110.1371/journal.pone.0120434