MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction

Nolting, A. et al. (2010) MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction. Virology, 406(1), pp. 12-20. (doi: 10.1016/j.virol.2010.05.014) (PMID:20667578) (PMCID:MC2932841)

Abstract

Natural killer (NK) cells play a critical role in host defense against viral infections. However chronic HIV-1 infection is associated with an accumulation of dysfunctional NK cells, that poorly control viral replication. The underlying mechanisms for this NK cell mediated dysfunction are not understood. Certain tumors evade NK cell mediated detection by dampening NK cell activity through the downregulation of NKG2D, via the release of soluble NKG2D-ligands, resulting in a potent suppression of NK cell function. Here we show that chronic HIV-1 infection is associated with a specific defect in NKG2D-mediated NK cell activation, due to reduced expression and transcription of NKG2D. Reduced NKG2D expression was associated with elevated levels of the soluble form of the NKG2D-ligand, MICA, in patient sera, likely released by HIV+CD4+ T cells. Thus, like tumors, HIV-1 may indirectly suppress NK cell recognition of HIV-1-infected CD4+ T cells by enhancing NKG2D-ligand secretion into the serum resulting in a profound impairment of NK cell function.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Rihn, Dr Suzannah
• Authors: Nolting, A., Dugast, A.-S., Rihn, S., Luteijn, R., Carrington, M. F., Kane, K., Jost, S., Toth, I., Nagami, E., Faetkenheuer, G., Hartmann, P., Altfeld, M., and Alter, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Virology
• Publisher: Elsevier Inc.
• ISSN: 0042-6822
• ISSN (Online): 1096-0341
• Copyright Holders: Copyright © 2010 Elsevier Inc.
• First Published: First published in Virology 406(1):12-20
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher