• Journal of Ginseng Research
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• 제43권2호
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• pp.312-318
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• 2019

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D. Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in $CD^{4+}$ T cell counts over $96{\pm}59months$ was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene. Results: $CD^{4+}$ T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment (p < 0.001). Of these, two subtype D-infected patients and 116 subtype B-infected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the $KRG-na{\ddot{i}}ve$ group irrespective of subtype (p < 0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype D-infected patients than in subtype B-infected patients (p < 0.01). KRG treatment had a greater effect on AD in subtype D-infected patients than in subtype B-infected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 $KRG-na{\ddot{i}}ve$ (p < 0.001) and all 163 (p < 0.01) patients infected with subtype D than subtype B. Conclusion: Subtype D infection is associated with a >2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.

• Journal of Ginseng Research
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• 제45권1호
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• pp.149-155
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• 2021

Background: We have reported that internal deletions in the nef, gag, and pol genes in HIV-1-infected patients are induced in those treated with Korean Red Ginseng (KRG). KRG delays the development of resistance mutations to antiretroviral drugs. Methods: The vif-vpr genes over 26 years in 20 hemophiliacs infected with HIV-1 from a single source were sequenced to investigate whether vif-vpr genes were affected by KRG and KRG plus highly active antiretroviral therapy (ART) (hereafter called GCT) and compared the results with our previous data. Results: A significantly higher number of in-frame small deletions were found in the vif-vpr genes of KRG-treated patients than at the baseline, in control patients, and in ART-alone patients (p < 0.001). These were significantly reduced in GCT patients (p < 0.05). In contrast, sequences harboring a premature stop codon (SC) were more significant in GCT patients (10.1%) than in KRG-alone patients, control (p < 0.01), and ART-alone patients (p = 0.078 for peripheral blood mononuclear cells). The proportion of SC in Vpr was similar to that in Vif, whereas the proportion of sequences revealing SC in the env-nef genes was significantly lower than that in the pol-vif-vpr genes (p < 0.01). The genetic distance was 1.8 times higher in the sequences harboring SC than in the sequences without SC (p < 0.001). Q135P in the vif gene is significantly associated with rapid progression to AIDS (p < 0.01). Conclusion: Our data show that KRG might induce sD in the vif-vpr genes and that vif-vpr genes are similarly affected by lethal mutations.

• Journal of Ginseng Research
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• 제43권4호
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• pp.684-691
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• 2019

Background: We have reported that defective nef and gag genes are induced in HIV-1-infected patients treated with Korean Red Ginseng (KRG). Methods: To investigate whether KRG treatment and highly active antiretroviral therapy (HAART) affect genetic defects in the pol gene, we amplified and sequenced a partial pol gene (p-pol) containing the integrase portion (1.2 kb) by nested PCR with sequential peripheral blood mononuclear cells over 20 years and compared it with those patients at baseline, in control patients, those taking ginseng-based combination therapy (GCT; KRG plus combinational antiretroviral therapy) and HAART alone. We also compared our findings to look for the full-length pol gene (pol) (3.0-kb) Results: Twenty-patients infected with subtype B were treated with KRG for $116{\pm}58months$ in the absence of HAART. Internal deletion in the pol gene (${\Delta}pol$) was significantly higher in the KRG group (11.9%) than in the control group and at baseline; its detection was significantly inhibited during GCT as much as during HAART. In addition, the ${\Delta}pol$ in p-pol significantly depended on the duration of KRG treatment. In pol, the proportion of ${\Delta}pol$ was significantly higher in the KRG group (38.7%) than in the control group, and it was significantly inhibited during GCT and HAART. In contrast, the proportion of stop codon appeared not to be affected by KRG treatment. The PCR success rate was significantly decreased with longer GCT. Conclusion: The proportion of ${\Delta}pol$ depends on template size as well as KRG treatment. HAART decreases the detection of ${\Delta}pol$.

• Biomolecules & Therapeutics
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• 제3권3호
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• pp.210-216
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• 1995

Partially purified water-soluble extract mixture from Ricini and Coptidis (named as RIC) showed to be a potent inhibitor of human immunodeficiency virus-1 (HIV-1) replication. RIC was evaluated for in vitro anti-HIV activity using SupTl and H9 cells infected by a recombinant virus (pSVCAT) containing chloramphenicol acetyltransferase (CAT) gene substituted for nef gene in the HIV-1 genome. RIC inhibited syncytiaformation of SupTl cells with a half maximal effective concentration, $IC_{50}$/, of 2.5 $\mu\textrm{g}$/mι and showed marked inhibition of CAT activity in the infected H9 cells and also suppressed reverse transcriptase (RT) activity in the supernatant of the infected H9 culture. However, RIC did not inhibit the activity of reverse transcriptase directly when it was mixed with the enzyme or with viral particles. Berberine, one of components of RIC, also showed similar anti-HIV activity as RIC did. The data suggest that there are active ingredients which mediate anti-HIV activity in RIC.

• Journal of Microbiology
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• 제44권6호
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• pp.655-659
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• 2006

Phylogenetic studies of nef, pol, and env gene sequences of HIV-1 isolated from Koreans suggested the presence of a Korean clade in which Korean sequences are clustered to the exclusion of foreign sequences. We attempted to identify and characterize the Korean clade using all vif gene sequences isolated from Koreans registered in the NCBI GenBank database (n = 233). Most (77 %) of the Korean isolates belonged to the Korean clade as a large subcluster in subtype B, designated the Korean clade subtype B ($K_{C}B$). $K_{C}B$ sequences were relatively homogenous compared to Korean subtype B sequences that did not belong to the $K_{C}B$ (non-Korean clade subtype B; $NK_{C}B$). Comparison of amino acid frequencies of $K_{C}B$ and $NK_{C}B$ sequences revealed several positions where the amino acid frequencies were significantly different. These amino acid residues were critical in separating $K_{C}B$ from $NK_{C}B$ or from foreign sequences, since substitution of these amino acids in $K_{C}B$ with the $NK_{C}B$ amino acids relocated the $K_{C}B$ sequences to $NK_{C}B$, and vice versa. Further analyses of $K_{C}B$ will help us to understand the origin and evolutionary history of $K_{C}B$.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2006년도 International Meeting of the Microbiological Society of Korea
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• pp.129-131
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• 2006

Through molecular phylogenetic analysis using the nef gene sequences of HIV-l isolated from Korean registered in the NCBI GenBank together with 41 reference strains and 94 foreign isolates, we verified that most (${\sim}80%$) of Korean isolates belonged to subtype B and 78% of subtype B were clustered together exclusively of foreign isolates, and this cluster was named Korean clade subtype B ($K_cB$). Similarity study suggested that the $K_cB$ cluster was more homogeneous than and clearly distinctive from the non-Korean subtype B ($NK_cB$). Comparison of the consensus amino acid sequences of the $K_cB\;or\;NK_cB$ revealed characteristic $K_cB$ signature amino acid pattern comprised of 13 amino acid residues. The $K_cB$ signature amino acid residues were critical in separating the $K_cB$ ftom the $NK_cB$, since substitution of the $NK_cB$ sequences with $K_cB$ signature amino acids relocated them to the Koran clade, and vice versa. Synonymous and nonsynonymous substitution rate study suggested positive selection event for the $K_cB$.

• 대한바이러스학회지
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• 제29권2호
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• pp.107-118
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• 1999

To characterize the molecular nature of human immunodeficiency virus (HIV)-1, we determined the full-length HIV-1 sequences from cultured peripheral blood mononuclear cells (PBMC) of a Korean long-term nonprogressor (LTNP). Without antiretroviral therapy, the individual has maintained CD4+ T counts over $500/{\mu}l$ from 1989 to 1999. Plasma viral RNA copy was 992 U/ml in 1998. Culture supernatant showed positive from culture days 9. A series of 9 overlapping PCR products were amplified from cultured PBMC and cloned About 9.2 kb from R of 5' LTR to R of 3' LTR was determined by automated sequencing. The G-to-A hypermutations were shown throughout the entire region. As a result of G to A hypermutations, premature stop codon was found in integrase coding region. Though there was no recombination between subtypes over all genomes, TATA box in both LTRs was TAAAA which is detected in subtype E instead of TATAA in subtype B. And, there were nucleotide GC insertion between $NF-{\kappa}B$ I and Sp1 III, and duplication of $TCF-1{\alpha}$ in LTR. We could not find any deletion of amino acid in Nef, Gag, Pol and Env gene. This study is the first report on molecular nature of full genomes of HIV-1 isolated in Korea.