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http://dx.doi.org/10.1016/j.jgr.2019.05.011

Korean Red Ginseng increases defective pol gene in peripheral blood mononuclear cells of HIV-1-infected patients; inhibition of its detection during ginseng-based combination therapy  

Cho, Young Keol (Department of Microbiology, University of Ulsan College of Medicine)
Kim, Jung-Eun (Department of Microbiology, University of Ulsan College of Medicine)
Woo, Jun-Hee (Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine)
Publication Information
Journal of Ginseng Research / v.43, no.4, 2019 , pp. 684-691 More about this Journal
Abstract
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 ${\Delta}pol$.
Keywords
AIDS; HIV-1; Korean Red Ginseng; Internal deletion; pol;
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1 Mutabingwa TK. Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy! Acta Trop 2005;95:305-15.   DOI
2 Li Y, Kappes JC, Conway JA, Price RW, Shaw GM, Hahn BH. Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol 1991;65:3973-85.   DOI
3 Sanchez G, Xu X, Chermann JC, Hirsch I. Accumulation of defective viral genomes in peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected individuals. J Virol 1997;71:2233-40.   DOI
4 Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-competent non-induced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 2013;155:540-51.   DOI
5 Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, Lai J, Strain MC, Lada SM, Hoh R, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med 2016;22:1043-9.   DOI
6 Hiener B, Horsburgh BA, Eden JS, Barton K, Schlub TE, Lee E, von Stockenstrom S, Odevall L, Milush JM, Liegler T, et al. Identification of genetically intact HIV-1 proviruses in specific CD4+ T cells from effectively treated participants. Cell Rep 2017;21:813-22.   DOI
7 Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 1995;267:483-9.   DOI
8 Huang Y, Zhang L, Ho DD. Characterization of gag and pol sequences from long-term survivors of human immunodeficiency virus type 1 infection. Virology 1998;240:36-49.   DOI
9 Zhang L, Huang Y, Yuan H, Tuttleton S, Ho DD. Genetic characterization of vif, vpr, and vpu sequences from long-term survivors of human immunodeficiency virus type 1 infection. Virology 1997;228:340-9.   DOI
10 Trabaud MA, Cotte L, Saison J, Ramiere C, Ronfort C, Venet F, Tardy JC, Monneret G, Andre P. Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient. AIDS Res Hum Retroviruses 2015;31:142-9.   DOI
11 Miura T, Brockman MA, Brumme CJ, Brumme ZL, Carlson JM, Pereyra F, Trocha A, Addo MM, Block BL, Rothchild AC, et al. Genetic characterization of human immunodeficiency virus type 1 in elite controllers: lack of internal genetic defects or common amino acid changes. J Virol 2008;82:8422-30.   DOI
12 Li CP, Li RC. An introductory note to ginseng. Am J Chin Med (Gard City N Y) 1973;1:249-61.
13 Deacon NJ, Tsykin A, Solomon A, Smith K, Ludford-Menting M, Hooker DJ, McPhee DA, Greenway AL, Ellett A, Chatfield C, et al. Genomic structure of an attenuated quasi species of HIV-1 from a blood transfusion donor and recipients. Science 1995;270:988-91.   DOI
14 Churchill MJ, Rhodes DI, Learmont JC, Sullivan JS, Wesselingh SL, Cooke IR, Deacon NJ, Gorry PR. Longitudinal analysis of human immunodeficiency virus type 1 nef/long terminal repeat sequences in a cohort of long-term survivors infected from a single source. J Virol 2006;80:1047-52.   DOI
15 Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 2007;27:406-16.   DOI
16 Sakure S, Negi VD, Mitra SK, Nandakumar KS, Chakravortty D. Vaccine with herbal adjuvantea better cocktail to combat the infection. Vaccine 2008;26:3387-8.   DOI
17 Rivera E, Ekholm Pettersson F, Inganas M, Paulie S, Gronvik KO. The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response. Vaccine 2005;23:5411-9.   DOI
18 Im K, Kim J, Min H. Ginseng, the natural effectual antiviral: protective effects of Korean Red Ginseng against viral infection. J Ginseng Res 2016 Oct;40(4):309-14.
19 Cho YK, Kim YB, Choi BS, Cho YJ, Suh IS, Shin YH. The increase of T cell by Korean red ginseng in HIV-infected individuals. J Korean Soc Microbiol 1994;29:371-9.
20 Cho YK, Kim YK, Lee I, Choi MH, Shin YO. The effect of Korean red ginseng (KRG), zidovudine (ZDV), and the combination of KRG and ZDV on HIVinfected patients. J Korean Soc Microbiol 1996;31:353-60.
21 Cho YK, Jung YS, Sung H. Frequent gross deletion in the HIV type 1 nef gene in hemophiliacs treated with Korean Red Ginseng: inhibition of detection by highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2009;25:419-24.   DOI
22 Cho YK, Kim YB, Kim YK, Lee HJ, Oh WI. Sequence analysis of C2-V3 region of human immunodeficiency virus type 1 gp120 and its correlation with clinical significance: the effect of long-term treatment of Korean red ginseng on env gene variation. J Korean Soc Microbiol 1997;32:611-23.
23 Cho YK, Sung HS. Effect of Korean red ginseng on serum soluble CD8 in HIV-1-infected patients. J Ginseng Res 2007;31:175-80.   DOI
24 Cho YK, Lim JY, Jung YS, Oh SK, Lee HJ, Sung H. High proportion of grossly deleted nef genes in HIV-1 infected long-term slow progressors treated with Korean red ginseng. Curr HIV Res 2006;4:447-57.   DOI
25 Cho YK, Kim JE, Woo JH. Genetic defects in the nef gene are associated with Korean Red Ginseng treatment: monitoring of nef sequence polymorphisms over 20 years. J Ginseng Res 2017;41:144-50.   DOI
26 Palella JrJr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998;338:853-60.   DOI
27 Cho YK, Sung H, Lee HJ, Joo CH, Cho GJ. Long-term treatment of Korean red ginseng in HIV-1-infected patients: development of resistance mutation to zidovudine is delayed. Int Immunopharmacol 2001;1:1295-305.   DOI
28 Cho YK, Sung H, Kim TK, Lim JY, Jung YS, Kang SM. Korean red ginseng significantly slows CD4 T cell depletion over 10 years in HIV-1 infected patients: association with HLA. J Ginseng Res 2004;28:173-82.   DOI
29 Cho YK, Jung YS. High proportion of gross deletions in the 5' LTR and gag regions in HIV type 1-infected long-term survivors treated with Korean Red Ginseng. AIDS Res Hum Retroviruses 2008;24:181-93.   DOI
30 Sung H, Kang SM, Lee MS, Kim TG, Cho YK. Korean red ginseng slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients. Clin Diagn Lab Immunol 2005;12:497-501.   DOI
31 Cho YK, Jung YS, Sung H, Sim MK, Kim YK. High proportion of gross deletions in 5' LTR/gag and nef genes in patients infected with CRF02_AG of HIV type 1 who survived for over 20 years: an association with Korean red ginseng. AIDS Res Hum Retroviruses 2009;25:535-41.   DOI
32 Cho YK, Jung YS. Dosage and duration effects of KRG treatment on proportion of gross deletions in the nef gene. J Ginseng Res 2010;34:219-25.   DOI
33 Cho YK, Jung Y, Sung H, Joo CH. Frequent genetic defects in the HIV-1 5'LTR/gag gene in hemophiliacs treated with Korean red ginseng; decreased detection of genetic defects by highly active antiretroviral therapy. J Ginseng Res 2011;35:413-20.   DOI
34 Sandonis V, Casado C, Alvaro T, Pernas M, Olivares I, Garcia S, Rodriguez C, del Romero J, Lopez-Galindez C. A combination of defective DNA and protective host factors are found in a set of HIV-1 ancestral LTNPs. Virology 2009;391:73-82.   DOI
35 Paolucci S, Gulminetti R, Maserati R, Dossena L, Baldanti F. Accumulation of defective HIV-1 variants in a patient with slow disease progression. Curr HIV Res 2011;9:17-22.   DOI
36 Sung H, Jung YS, Cho YK. Beneficial effects of a combination of Korean red ginseng and highly active antiretroviral therapy in human immunodeficiency virus type 1-infected patients. Clin Vaccine Immunol 2009;16:1127-31.   DOI
37 Imamichi H, Dewar RL, Adelsberger JW, Rehm CA, O'Doherty U, Paxinos EE, Fauci AS, Lane HC. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci USA 2016;113:8783-8.   DOI
38 Cho YK, Jung Y, Foley BT. Phylogenetic analysis of full-length pol gene from Korean hemophiliacs and plasma donors infected with Korean subclade B of HIV-1. AIDS Res Hum Retroviruses 2011;27:613-21.   DOI
39 Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 1995;373:123-6.   DOI
40 Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 1995;373:117-22.   DOI
41 Sanchez G, Gautheret D, Xu X, Chenine AL, Hirsch I. Relative amplification efficiency of differently sized templates by long-distance PCR. BioTechniques 1998;24:400-2.   DOI
42 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-93.   DOI
43 Simoes CM, Amoros M, Girre L. Mechanisms of antiviral activity of triterpenoid saponins. Phytotherapy Res 1999;13:323-8.   DOI
44 Wei Y, Ma CM, Hattori M. Anti-HIV protease triterpenoids from the acid hydrolysate of Panax ginseng. Phytochem Lett 2009;2:63-6.   DOI
45 Zhang H, Lu Z, Tan GT. Polyacetylenginseng-Ro, a novel triterpene saponin from Panax ginseng. Tetrahedron Lett 2002;43:973-7.   DOI
46 Nakaya TA, Kita M, Kuriyama H, Iwakura Y, Imanishi J. Panax ginseng induces production of proinflammatory cytokines via toll-like receptor. J Interferon Cytokine Res 2004;24:93-100.   DOI
47 Lam SK, Ng TB. A xylanase from roots of sanchi ginseng (Panax notoginseng) with inhibitory effects on human immunodeficiency virus-1 reverse transcriptase. Life Sci 2002;70:3049-58.   DOI
48 See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997;35:229-35.   DOI
49 Ahn JY, Choi IS, Shim JY, Yun EK, Yun YS, Jeong G, Song JY. The immunomodulator ginsan induces resistance to experimental sepsis by inhibiting Tolllike receptor-mediated inflammatory signals. Eur J Immunol 2006;36:37-45.   DOI
50 Kim KH, Lee YS, Jung IS, Park SY, Chung HY, Lee IR, Yun YS. Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta Med 1998;64:110-5.   DOI
51 Larsen MW, Moser C, Hoiby N, Song Z, Kharazmi A. Ginseng modulates the immune response by induction of interleukin-12 production. APMIS 2004;112:369-73.   DOI
52 Yang CS, Yuk JM, Ko SR, Cho BG, Sohn HJ, Kim YS, Wee JJ, Do JH, Jo EK. Compound K rich fractions regulate $NF-{\kappa}_{B}-dependent$ inflammatory responses and protect mice from endotoxin-induced lethal shock. J Ginseng Res 2008;32:315-23.   DOI
53 Chaillon A, Gianella S, Lada SM, Perez-Santiago J, Jordan P, Ignacio C, Karris M, Richman DD, Mehta SR, Little SJ, et al. Size, composition, and evolution of HIV DNA populations during early antiretroviral therapy and intensification with maraviroc. J Virol 2018;92. e01589-17.
54 Rawson JMO, Nikolaitchik OA, Keele BF, Pathak VK, Hu WS. Recombination is required for efficient HIV-1 replication and the maintenance of viral genome integrity. Nucleic Acids Res 2018;16:10535-45.