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Correction published on 5 October 2012, see Viruses 2012, 4(10), 2014-2015.

Viruses 2012, 4(9), 1711-1730; doi:10.3390/v4091711
Review

Human Leukocyte Antigen (HLA) Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef): What Might We Learn From Natural Sequence Variants?

1
,
1
,
2
 and
1,3,*
1 Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada 2 Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan 3 Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada
* Author to whom correspondence should be addressed.
Received: 31 August 2012 / Revised: 18 September 2012 / Accepted: 21 September 2012 / Published: 24 September 2012
(This article belongs to the Special Issue Immune Evasion)
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Abstract

HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome.
Keywords: HIV-1; Nef; immune evasion; HLA class I; cytotoxic T lymphocyte; viral sequence diversity; host immune selection pressure HIV-1; Nef; immune evasion; HLA class I; cytotoxic T lymphocyte; viral sequence diversity; host immune selection pressure
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Mwimanzi, P.; Markle, T.J.; Ueno, T.; Brockman, M.A. Human Leukocyte Antigen (HLA) Class I Down-Regulation by Human Immunodeficiency Virus Type 1 Negative Factor (HIV-1 Nef): What Might We Learn From Natural Sequence Variants? Viruses 2012, 4, 1711-1730.

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