Abstract
The Nef protein is a major determinant of pathogenicity caused by the Human Immunodeficiency virus (HIV) and is encoded by the nef gene within the genomes of primate lentiviruses HIV-1, HIV-2 and simian immunodeficiency virus (SIV). The HIV Nef protein subverts the intracellular membrane traffic to mediate endocytosis of a number of cell surface receptors to accelerate their degradation. In this review we will examine how the multifunctional Nef protein can mediate downregulation of the Major Histocompatibility Complex (MHC) I proteins from the surface of infected cells as a means of immune evasion by HIV. By selectively downregulating MHC-I HLA-A and HLA-B haplotypes, while maintaining the expression of HLA-C, HLA-E and HLA-G the HIV virus is able to avoid recognition by both the NK and cytotoxic CD8+ T cell effector responses. This protects the virus from cell lysis and enables it to hide from the cell-mediated immune system.
Highlights
The human immunodeficiency virus (HIV) is a major global health issue that has claimed 39 million lives since its discovery in 1983 [1,2]
The Nef protein has a wide range of functions unrelated to infectivity of virions, some of those which are directly related to immune evasion such as down modulation of CD4 [38,39], Major histocompatibility Complex (MHC)-I [30,78] and to modulate the threshold of T cell activation between T cells and macrophages [79,80]
The ability of Nef to interfere with the MHC-I complex is an important virulence factor as it enables the HIV virus to evade the host immune response
Summary
The human immunodeficiency virus (HIV) is a major global health issue that has claimed 39 million lives since its discovery in 1983 [1,2]. In 2013 HIV had a worldwide incidence of 2.1 million cases and a prevalence of approximately 35 million individuals [2]. The virus arose from cross-species transmission with HIV-1 originating from the chimpanzee simian immunodeficiency virus (SIVcpz) and HIV-2 arising from the sooty mangabey virus (SIVsmm) [1]. As a result of the different origins of HIV-1 and HIV-2 their nucleic acid sequences are only 40% homologous and HIV-2 is less virulent with 98% of acquired immunodeficiency syndrome (AIDS) cases arising from HIV-1 infection [1]. Group M is the most virulent and is responsible for 90% of the AIDS epidemic worldwide with Group O and N remaining confined within Africa [3,4]
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