The Chinese herb-derived Sparstolonin B suppresses HIV-1 transcription

Virology Journal

Jian Liang¹  Bin Wen¹  Peichun Peng¹  Ran Chen¹  Feng Jiang¹  Yaping Zhang¹  Xin Deng¹ 

[1] Department of Infectious Diseases, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, 10 Huadong Road, Nanning, 530011, Guangxi Province, China

关键词: TAR region;    HIV transcription;    Sparstolonin B;   

Others  :  1224900
DOI  :  10.1186/s12985-015-0339-8

 received in 2015-02-18, accepted in 2015-07-03,  发布年份 2015

【 摘 要 】

Background

The Chines herb derived Sparstolonin B, (SsnB), is a recently identified natural compound that selectively blocks TLR2- and TLR4-mediated inflammatory signaling. But it is unknown whether this compound has any effect on HIV infection.

Findings

We found that SsnB treatment blocked HIV-1 transcription via a novel mechanism that requires the TAR region. Treatment of human T cell lines or peripheral blood mononuclear cells with SsnB at 1 μM significantly inhibited HIV production. Lastly, SsnB was able to inhibit HIV in synergy with AZT.

Conclusions

These data suggest that SsnB is a novel natural compound that inhibits HIV-1 transcription and may be a new drug in the treatment of HIV infection.

【 授权许可】

   
2015 Deng et al.

【 图 表 】

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【 参考文献 】

• [1]Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990; 61(2):213-22.
• [2]Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M. Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection. Science. 1991; 254(5030):423-7.
• [3]McDougal JS, Mawle A, Cort SP, Nicholson JK, Cross GD, Scheppler-Campbell JA et al.. Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985; 135(5):3151-62.
• [4]Ganesh L, Burstein E, Guha-Niyogi A, Louder MK, Mascola JR, Klomp LW et al.. The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes. Nature. 2003; 426(6968):853-7.
• [5]Qiu C, Xu X. H. Z. Pharmacology and clinics of Chinese material. Medica. 2008;14.
• [6]Lee SY, Choi SU, Lee JH, Lee DU, Lee KR. A new phenylpropane glycoside from the rhizome of Sparganium stoloniferum. Arch Pharm Res. 2010; 33(4):515-21.
• [7]Liang Q, Wu Q, Jiang J, Duan J, Wang C, Smith MD et al.. Characterization of sparstolonin B, a Chinese herb-derived compound, as a selective Toll-like receptor antagonist with potent anti-inflammatory properties. J Biol Chem. 2011; 286(30):26470-9.
• [8]Wei X, Decker JM, Liu H, Zhang Z, Arani RB, Kilby JM et al.. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob Agents Chemother. 2002; 46(6):1896-905.
• [9]Garcia JA, Harrich D, Soultanakis E, Wu F, Mitsuyasu R, Gaynor RB. Human immunodeficiency virus type 1 LTR TATA and TAR region sequences required for transcriptional regulation. Embo J. 1989; 8(3):765-78.
• [10]Southgate CD, Green MR. The HIV-1 Tat protein activates transcription from an upstream DNA-binding site: implications for Tat function. Genes Dev. 1991; 5(12B):2496-507.
• [11]Shridhar V, Chen Y, Gupta P. The CD8 antiviral factor (CAF) can suppress HIV-1 transcription from the long terminal repeat (LTR) promoter in the absence of elements upstream of the CATATAA box. Virol J. 2014; 11:130. BioMed Central Full Text
• [12]Dingwall C, Ernberg I, Gait MJ, Green SM, Heaphy S, Karn J et al.. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc Natl Acad Sci U S A. 1989; 86(18):6925-9.
• [13]Weeks KM, Ampe C, Schultz SC, Steitz TA, Crothers DM. Fragments of the HIV-1 Tat protein specifically bind TAR RNA. Science. 1990; 249(4974):1281-5.
• [14]Roy S, Delling U, Chen CH, Rosen CA, Sonenberg N. A bulge structure in HIV-1 TAR RNA is required for Tat binding and Tat-mediated trans-activation. Genes Dev. 1990; 4(8):1365-73.
• [15]Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010; 85(1):1-18.
• [16]Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010; 70(2):440-6.
• [17]Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev. 1995; 47(2):331-85.
• [18]Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 1984; 22:27-55.
• [19]Eron JJ, Johnson VA, Merrill DP, Chou TC, Hirsch MS. Synergistic inhibition of replication of human immunodeficiency virus type 1, including that of a zidovudine-resistant isolate, by zidovudine and 2’,3’-dideoxycytidine in vitro. Antimicrob Agents Chemother. 1992; 36(7):1559-62.