Modest attenuation of HIV-1 Vpu alleles derived from elite controller plasma
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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 20, 2015
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| In: |
PLOS ONE
Year: 2015, Volume: 10, Issue: 3 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0120434 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pone.0120434 Verlag, kostenfrei, Volltext: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368696/ 
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| Author Notes: | 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 |
| Summary: | 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 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. |
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| Item Description: | Gesehen am 23.08.2017 |
| Physical Description: | Online Resource |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0120434 |