Effects of Korean Red Ginseng and HAART on vif Gene in 10 Long-Term Slow Progressors over 20 Years: High Frequency of Deletions and G-to-A Hypermutation

Abstract

To investigate if Korean red ginseng (KRG) affects vif gene, we determined vif gene over 20 years in 10 long-term slowly progressing patients (LTSP) who were treated with KRG alone and then KRG plus HAART. We also compared these data with those of 21 control patients who did not receive KRG. Control patient group harbored only one premature stop codon (PSC) (0.9%), whereas the 10 LTSP revealed 78 defective genes (18.1%) (P < 0.001). The frequency of small in-frame deletions was found to be significantly higher in patients who received KRG alone (10.5%) than 0% in the pre-KRG or control patients (P < 0.01). Regarding HAART, vif genes containing PSCs were more frequently detected in patients receiving KRG plus HAART than patients receiving KRG alone or control patients (P < 0.01). In conclusion, our current data suggest that the high frequency of deletions and PSC in the vif gene is associated with KRG intake and HAART, respectively.

Figure 1

Changes in the CD4+ T-cell count, plasma viral load, and genetic defects in terms of Korean red ginseng (KRG) intake and highly active antiretroviral therapy (HAART). The durations of KRG intake and HAART are indicated by the bars. Solid and dotted lines denote good (>90%) and poor (<90%) compliance according to self-administered responses, respectively. The upward arrow (↑), downward arrow (↓), plus sign (+), and asterisk (∗) denote the sequences of the vif gene, gross deletions, 3- and- 6-base pair (bp) in-frame insertions, and stop codons, respectively.

Figure 2

Sequential alignment of the amino acids of the Vif protein over 20 years. All sequences that demonstrated small in-frame deletions, gross deletions, and stop codons are depicted together with the baseline and last sequences of each patient. Patients 90-18 demonstrated a 9 bp deletion (positions 182–184) in April 1998, and patient 92-13 demonstrated a 12 bp deletion (positions 185–188) in May 2005. Patient 90-05 consistently demonstrated a 9 bp insertion (RQTRAR-RAR-NGASRP) at the same position at the terminus of vpr beginning in August 2000 (data not shown). The code 92LSH3-6951 (sampling year, initials of the patient, sampling month, and sequence number) denotes that the sampling date is March 1992 and the sequence number is 6951 in patient LSH (90-18). The dot (·), hyphen (-), and asterisk (∗) denote sequence identity, deletions, and premature stop codons, respectively, compared with the Korean consensus [20]. In the right column, the plus (+) and minus (−) signs denote the presence or absence of the corresponding therapy, respectively.

Figure 3

Positions of the premature stop codons in the 15 vif genes from five patients. All stop codons resulted from GG → GA or GG → AG changes. APOBEC3G exhibits an intrinsic preference for the second cytosine in a 5′CC dinucleotide motif leading to 5′GG-to-AG mutations [38].