Analysis of the HIV-1nef gene in five intravenous drug users with long-term nonprogressive HIV-1 infection in Italy

Abstract

Great variability in the course of human immunodeficiency virus type 1 (HIV-1) infection results from a complex interplay between host and virus factors. Some of the patients with prolonged nonprogressive infection have been reported to harbor virus variants with gross deletions in the accessory nef gene that has been implicated in in vivo pathogenicity in simian and mouse models. To investigate the role of nef-deleted HIV-1 in long-term nonprogressor (LTNP) drug addicts in Italy the nef sequence from proviral DNA was analyzed from five LTNPs and five rapid progressor controls. Only small (2-12 amino acids) in-frame deletions and insertions were detected in the N-terminal polymorphic and variable regions obtained from three LTNPs and one rapid progressor. There was no evidence of premature termination of the Nef protein and all of the identified functional motifs were well conserved in both groups. Phylogenetic analysis showed interdigitation of nef sequences obtained from LTNPs and rapid progressors. The nef sequence of one LTNP, however, diverged significantly from those of the other patients. Availability of two additional blood DNA samples obtained previously from this subject allowed to detect evolution of nef at 14-17 years of HIV-1 infection, including progressive deletions. Although alterations of nef may be relatively frequent and continue to evolve in LTNPs, this study of a small number of patients does not indicate that gross deletions or loss of functional motifs play a major role in delaying or halting disease progression in infected drug abusers in Italy.

Morphine and Rapid Disease Progression in Nonhuman Primate Model of AIDS: Inverse Correlation Between Disease Progression and Virus Evolution

“…However, the study was complicated by the existence of potential functional defects in the vpr gene, as well as the inability of polymerase chain reaction to amplify a fragment of nef at a variety of time points over to course of infection (Saksena et al 1996). In contrast, a study of five HIV-positive intravenous drug users in Italy, all of whom were long-term survivors, demonstrated only a single individual with detectable alterations (deletions) of nef that would lead to loss of function (Catucci et al 2000). Thus, the studies in drug abusing humans do not provide a clear indication of the specific role of Nef in pathogenesis.…”

Quality Evaluation of College Physical Training considering Apriori Algorithm

“…With the continuous advancement in the society and economy, more and more attention has been paid to physical training. It is necessary to ensure the growth of students as the primary subjects of education in their studies and physical tness on all fronts [1][2][3]. However, due to the excessive academic load, the vast majority of students cannot obtain a proper degree of exercise.…”

Proteomic Profiling of SupT1 Cells Reveal Modulation of Host Proteins by HIV-1 Nef Variants

“…Thus, sequence variation will contribute to structure based functional analysis of Nef and in understanding how the Nef variants vary in their regulatory role with host proteins. Nef contributes to disease progression and different stages of infection reveal specific Nef mutations [ 10 – 12 ]. Several studies have analysed Nef gene in HIV-1 patient’s population.…”