@article{oai:nagasaki-u.repo.nii.ac.jp:00004189, author = {Chen, Jingyan and Tibroni, Nadine and Sauter, Daniel and Galaski, Johanna and Miura, Toshiyuki and Alter, Galit and Mueller, Birthe and Haller, Claudia and Walker, Bruce D. and Kirchhoff, Frank and Brumme, Zabrina L. and Ueno, Takamasa and Fackler, Oliver T.}, issue = {3}, journal = {PLOS ONE}, month = {Mar}, note = {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-eκB 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., PLOS ONE, 10(3), e0120434; 2015}, title = {Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma}, volume = {10}, year = {2015} }