Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Cho, Young-Keol (Department of Microbiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Jung, You-Sun (Department of Microbiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Sung, Heung-Sup (Department of Microbiology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Joo, Chul-Hyun (Department of Microbiology, Asan Medical Center, University of Ulsan College of Medicine)
  • Received : 2011.02.21
  • Accepted : 2011.08.11
  • Published : 2011.12.26
Download PDF
⟨ Previous Next ⟩

Abstract

We investigated whether Korean red ginseng (KRG) and highly active antiretroviral therapy (HAART) affect the frequency of gross deletion in 5'LTR/gag in 20 hemophiliacs. This study is a prospective study in 20 hemophiliacs who were infected with Korean subclade B of HIV-1 from two cash-paid plasma donors in 1990. Over a 13-year period, we obtained 436 amplicons of 5'LTR/gag genes by nested polymerase chain reaction using 147 peripheral blood mononuclear cells. Of the 436 amplicons, 92 (21.1%) showed gross deletion in 5'LTR/gag. Despite of a 2.3-fold higher monthly dose of KRG intake, the frequency of gross deletion in 5'LTR/gag (16.4%) was significantly decreased during HAART compared with 28.1% prior to HAART (p<0.01). Gross deletion in 5'LTR/gag was 10% more detected on KRG-therapy than prior to KRG-therapy (p<0.05). In addition, we also obtained 28 amplicons containing premature stop codon or isoleucine at initiation codon of 254 amplicons sequenced on KRG intake (7.5%) or HAART (13.6%) compared with 0% before KRG intake. These findings indicate that high frequency of gross deletion in 5'LTR/gag and genetic defects prior to HAART are significantly associated with KRG intake and the detection of gross deletion in 5'LTR/gag is decreased by HAART.

Keywords

References

  1. Li CP, Li RC. An introductory note to ginseng. Am J Chin Med (Gard City N Y) 1973;1:249-261. https://doi.org/10.1142/S0192415X73000279
  2. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  3. Kim DH. Metabolism of ginsenosides to bioactive compounds by intestinal microflora and its industrial application. J Ginseng Res 2009;33:165-176. https://doi.org/10.5142/JGR.2009.33.3.165
  4. Singh VK, Agarwal SS, Gupta BM. Immunomodulatory activity of Panax ginseng extract. Planta Med 1984;50:462-465. https://doi.org/10.1055/s-2007-969773
  5. Fulder SJ. Ginseng and the hypothalamic-pituitary control of stress. Am J Chin Med 1981;9:112-118. https://doi.org/10.1142/S0192415X81000159
  6. Song X, Hu S. Adjuvant activities of saponins from traditional Chinese medicinal herbs. Vaccine 2009;27:4883-4890. https://doi.org/10.1016/j.vaccine.2009.06.033
  7. Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicine-ginseng (II): collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr Med Chem 2009;16:2924-2942. https://doi.org/10.2174/092986709788803204
  8. Gao H, Wang F, Lien EJ, Trousdale MD. Immunostimulating polysaccharides from Panax notoginseng. Pharm Res 1996;13:1196-1200. https://doi.org/10.1023/A:1016060119425
  9. Rivera E, Hu S, Concha C. Ginseng and aluminium hydroxide act synergistically as vaccine adjuvants. Vaccine 2003;21:1149-1157. https://doi.org/10.1016/S0264-410X(02)00518-2
  10. Hu S, Concha C, Lin F, Persson Waller K. Adjuvant effect of ginseng extracts on the immune responses to immunisation against Staphylococcus aureus in dairy cattle. Vet Immunol Immunopathol 2003;91:29-37. https://doi.org/10.1016/S0165-2427(02)00264-7
  11. Sun HX, Ye YP, Pan HJ, Pan YJ. Adjuvant effect of Panax notoginseng saponins on the immune responses to ovalbumin in mice. Vaccine 2004;22:3882-3889. https://doi.org/10.1016/j.vaccine.2004.04.012
  12. Sun H, Ye Y, Pan Y. Immunological-adjuvant saponins from the roots of Panax notoginseng. Chem Biodivers 2005;2:510-515. https://doi.org/10.1002/cbdv.200590032
  13. Qin F, Ye YP, Sun HX. Haemolytic activity and adjuvant effect of notoginsenoside K from the roots of Panax notoginseng. Chem Biodivers 2006;3:1144-1152. https://doi.org/10.1002/cbdv.200690116
  14. Sun J, Hu S, Song X. Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice. Vaccine 2007;25:1114-1120. https://doi.org/10.1016/j.vaccine.2006.09.054
  15. Kirchhoff F, Greenough TC, Brettler DB, Sullivan JL, Desrosiers RC. Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med 1995;332:228-232. https://doi.org/10.1056/NEJM199501263320405
  16. 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;270:988-991. https://doi.org/10.1126/science.270.5238.988
  17. Mariani R, Kirchhoff F, Greenough TC, Sullivan JL, Desrosiers RC, Skowronski J. High frequency of defective nef alleles in a long-term survivor with nonprogressive human immunodeficiency virus type 1 infection. J Virol 1996;70:7752-7764.
  18. Rhodes DI, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N. Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group. J Virol 2000;74:10581-10588. https://doi.org/10.1128/JVI.74.22.10581-10588.2000
  19. Brambilla A, Turchetto L, Gatti A, Bovolenta C, Veglia F, Santagostino E, Gringeri A, Clementi M, Poli G, Bagnarelli P et al. Defective nef alleles in a cohort of hemophiliacs with progressing and nonprogressing HIV-1 infection. Virology 1999;259:349-368. https://doi.org/10.1006/viro.1999.9783
  20. Rodes B, Toro C, Paxinos E, Poveda E, Martinez-Padial M, Benito JM, Jimenez V, Wrin T, Bassani S, Soriano V. Differences in disease progression in a cohort of long-term non-progressors after more than 16 years of HIV-1 infection. AIDS 2004;18:1109-1116. https://doi.org/10.1097/00002030-200405210-00004
  21. Roger M. Influence of host genes on HIV-1 disease progression. FASEB J 1998;12:625-632. https://doi.org/10.1096/fasebj.12.9.625
  22. Salvi R, Garbuglia AR, Di Caro A, Pulciani S, Montella F, Benedetto A. Grossly defective nef gene sequences in a human immunodeficiency virus type 1-seropositive long-term nonprogressor. J Virol 1998;72:3646-3657.
  23. 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 gross genetic defects or common amino acid changes. J Virol 2008;82:8422-8430. https://doi.org/10.1128/JVI.00535-08
  24. Cho YK, Lim JY, Jung YS, Oh SK, Lee HJ, Sung H. High frequency of grossly deleted nef genes in HIV-1 infected long-term slow progressors treated with Korean red ginseng. Curr HIV Res 2006;4:447-457. https://doi.org/10.2174/157016206778560072
  25. Cho YK, Jung YS. High frequency 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;24:181-193. https://doi.org/10.1089/aid.2007.0143
  26. 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;25:419-424. https://doi.org/10.1089/aid.2008.0178
  27. Cho YK, Jung YS, Sung H, Sim MK, Kim YK. High frequency 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;25:535-541. https://doi.org/10.1089/aid.2008.0301
  28. Cho YK, Jung YS. Dosage and duration effects of Korean red ginseng intake on frequency of gross deletions in the nef gene. J Ginseng Res 2010;34:219-225. https://doi.org/10.5142/jgr.2010.34.3.219
  29. Cho YK, Foley BT, Sung H, Kim YB, Kim JH. Molecular epidemiologic study of a human immunodeficiency virus 1 outbreak in haemophiliacs B infected through clotting factor 9 after 1990. Vox Sang 2007;92:113-120. https://doi.org/10.1111/j.1423-0410.2006.00866.x
  30. Cho YK, Sung H, Kim TK, Lim J, 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;28:173-182. https://doi.org/10.5142/JGR.2004.28.4.173
  31. 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.
  32. 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. https://doi.org/10.1006/viro.1997.8913
  33. Calugi G, Montella F, Favalli C, Benedetto A. Entire genome of a strain of human immunodeficiency virus type 1 with a deletion of nef that was recovered 20 years after primary infection: large pool of proviruses with deletions of env. J Virol 2006;80:11892-11896. https://doi.org/10.1128/JVI.00932-06
  34. Blankson JN, Siliciano RF. Elite suppression of HIV-1 replication. Immunity 2008;29:845-847. https://doi.org/10.1016/j.immuni.2008.12.002
  35. Blankson JN. Effector mechanisms in HIV-1 infected elite controllers: highly active immune responses? Antiviral Res 2010;85:295-302. https://doi.org/10.1016/j.antiviral.2009.08.007

Cited by

  1. Long-term follow up of HIV-1-infected Korean haemophiliacs, after infection from a common source of virus vol.21, pp.1, 2014, https://doi.org/10.1111/hae.12527
  2. Phylogenetic Analysis of Near Full-Length HIV Type 1 Genomic Sequences from 21 Korean Individuals vol.29, pp.4, 2013, https://doi.org/10.1089/aid.2012.0298
  3. Ginseng, the 'Immunity Boost': The Effects of Panax ginseng on Immune System vol.36, pp.4, 2011, https://doi.org/10.5142/jgr.2012.36.4.354
  4. 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 vol.2013, pp.None, 2011, https://doi.org/10.1155/2013/871648
  5. Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection vol.40, pp.4, 2011, https://doi.org/10.1016/j.jgr.2015.09.002
  6. Protective roles of ginseng against bacterial infection vol.5, pp.11, 2011, https://doi.org/10.15698/mic2018.11.654