Nef Alleles from Human Immunodeficiency Virus Type 1-InfectedLong-Term-Nonprogressor Hemophiliacs with or without Late Disease Progression Are Defective in Enhancing Virus Replication and CD4 Down-Regulation

Abstract

Infection with human immunodeficiency virus (HIV)-encoding defective

Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression

“…Some studies have shown that virus strains from LTNPs are less evolved and thus less capable of evading the host immunological response when compared with progressor strains (Sandonís et al, 2009;Wang et al, 2003). The classic example of HIV-1 LTNP virus attenuation is the Sydney Blood Bank cohort (n58), whose members were infected from blood transfusions from the same donor infected with an HIV-1 strain that contained a large Mechanisms of control in HIV-1 LTNPs deletion in a long-terminal repeat from a conserved and biologically significant area in the nef gene (Crotti et al, 2006;Learmont et al, 1999). Six of the subjects went on to become LTNPs and maintained stable CD4 + T-cell levels and low viral loads for over 10 years.…”

Nef-Mediated Enhancement of Virion Infectivity and Stimulation of Viral Replication Are Fundamental Properties of Primate Lentiviruses

“…It has been suggested that Nef-mediated CD4 downmodulation (26,39) and/or activation of resting T cells (2,19,64,74) contributes to its enhancing effect on viral replication. Importantly, studies in the SIV/macaque model and the functional analysis of nef alleles from long-term survivors of HIV-1 infection suggest that both Nef activities are relevant for efficient viral persistence and the pathogenesis of AIDS in vivo (7,10,15,19,32,41,73).…”

Functions of the Lentiviral Accessory Protein Nef During the Distinct Steps of HIV and SIV Replication Cycle

“…Moreover, Nef also down-regulates other cell-surface proteins, as the major histocompatibility complex class I (MHC-I) molecules (Greenberg et al, 1998b;Swigut et al, 2000). Observations from naturally HIV-1-infected individuals indicated that Nef functions on downmodulation of CD4 and MHC-I could be related to the pathogenesis of AIDS (Carl et al, 2001;Tobiume et al, 2002), however the real contribution of these functions still needs to be demonstrated (Crotti et al, 2006). The motifs in Nef that mediate CD4 downregulation were considered critical for SIVmac replication in rhesus macaques, however MHC-I downregulation by Nef is not sufficient for optimal virulence of SIVmac early in infection Lang et al, 1997;Schindler et al, 2004).…”