Genetic defects in the nef gene are associated with Korean Red Ginseng intake: monitoring of nef sequence polymorphisms over 20 years

Abstract

Background: The presence of gross deletions in the human immunodeficiency virus nef gene (gΔnef) is associated with long-term nonprogression of infected patients. Here, we investigated how quickly genetic defects in the nef gene are associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors.

Methods: This study was divided into three phases over a 20-yr period; baseline, KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene amplicons were obtained using reverse transcription polymerase chain reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and these were then sequenced. The proportion of gΔnef, premature stop codons, and not in-frame insertion or deletion of a nucleotide was compared between three phases, control, and ART patients.

Results: The proportion of defective nef genes was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p < 0.01). Small in-frame deletions or insertions were significantly more frequent among patients treated with KRG alone compared with controls (p < 0.01). Significantly fewer instances of genetic defects were detected in samples taken during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected were gΔnef and small in-frame deletions after 7 mo and 67 mo of KRG intake, respectively.

Conclusion: KRG treatment might induce genetic defects in the nef gene. This report provides new insight into the importance of genetic defects in the pathogenesis of AIDS.

Keywords: AIDS/HIV-1; Korean Red Ginseng; genetic defects; gross deletion; nef.

Fig. 1

Changes in the CD4+ T cell count, plasma viral load, and genetic defects according to Korean Red Ginseng (KRG) intake and highly active antiretroviral therapy (ART). The periods of KRG intake and ART, and duration of survival from diagnosis to initiation of ART are shown using a bar at the upper and middle parts, respectively. To our knowledge, Patient 87-05 is the longest follow-up case in the absence of ART in the literature. Patient 91-20 had a history of admission under suspicion of typhoid fever and blood donation on October 28, 1989. His blood recipients were infected with human immunodeficiency virus-1. The downward arrow (↓), ▲, ®, dotted line in the highest position (--), and asterisk (*) symbols at the base of the figure denote gross deletion, wild-type amplicon only, reverse transcription PCR, poor compliance, and premature stop codon, respectively. GCT, Korean Red Ginseng based combination therapy with ART; PCR, polymerase chain reaction.

Fig. 2

Comparison of the proportion of genetic defects such as gross deletion in the nef gene, not in-frame insertion or deletion, and premature stop codon. The proportion of genetic defects was significantly higher during Korean Red Ginseng (KRG) intake than in controls or at baseline and decreased significantly during GCT [KRG plus antiretroviral therapy (ART)]. In 28 ART patients, the numbers of gross deletions in the nef gene and stop codons were six (3.6%) and five (3.0%) of 165 amplicons, respectively.

Fig. 3

The proportion of genetic defects in the nef gene depends on the duration of Korean Red Ginseng (KRG) intake (p < 0.001). There was no defective gene 3–6 mo after KRG treatment (0/68). Genetic defects increased significantly after 12 mo compared with baseline (p < 0.05).