The Chinese herb-derived Sparstolonin B suppresses HIV-1 transcription
© Deng et al. 2015
Received: 18 February 2015
Accepted: 3 July 2015
Published: 25 July 2015
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.
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.
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.
KeywordsSparstolonin B HIV transcription TAR region
Despite the success of highly active antiretroviral therapy (HAART) in containing human immunodeficiency virus (HIV) infection, there has been an urgent demand for cheaper and alternative drugs in developing countries. Moreover, HIV persists in stable reservoirs harboring chromosomally integrated latent HIV-1 proviruses, where continuous viral production and reactivation of transcription from these reservoirs are not affected by current drugs [1–4]. As such, novel classes of antivirals are needed to inhibit these processes. In this regard, a drug that blocks HIV transcription would be of great value because it offers the potential to shut down the transcription in HIV latent reservoirs.
Synergism between SsnB and AZT
CI at HIV-1 inhibition of:
0.04, 0.16, 0.64, 1.28
0.1, 0.5, 1, 10
0.0025, 0.005, 0.01, 0.02
0.5, 1, 10, 50
This study was sponsored by National Natural Science Foundation of China Grant 2014DFA30580, The Ministry of Education of the People’s Republic of China grant NCET-13-0745, Guangxi Science and Technology key projects 1298003-1-1, 1355006–7, and 14124004-2-2. J. L. is a Guangxi Bagui Scholar.
- 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.PubMedView ArticleGoogle Scholar
- 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.PubMedView ArticleGoogle Scholar
- 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.PubMedGoogle Scholar
- 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. doi:10.1038/nature02171.PubMedView ArticleGoogle Scholar
- Qiu C, Xu X. H. Z. Pharmacology and clinics of Chinese material. Medica. 2008;14.Google Scholar
- 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. doi:10.1007/s12272-010-0404-1.PubMedView ArticleGoogle Scholar
- 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. doi:10.1074/jbc.M111.227934.PubMed CentralPubMedView ArticleGoogle Scholar
- 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.PubMed CentralPubMedView ArticleGoogle Scholar
- 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.PubMed CentralPubMedGoogle Scholar
- 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.PubMedView ArticleGoogle Scholar
- 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. doi:10.1186/1743-422X-11-130.PubMed CentralPubMedView ArticleGoogle Scholar
- 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.PubMed CentralPubMedView ArticleGoogle Scholar
- 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.PubMedView ArticleGoogle Scholar
- 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.PubMedView ArticleGoogle Scholar
- Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res. 2010;85(1):1–18. doi:10.1016/j.antiviral.2009.10.002.PubMed CentralPubMedView ArticleGoogle Scholar
- Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–6. doi:10.1158/0008-5472.CAN-09-1947.PubMedView ArticleGoogle Scholar
- 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.PubMedGoogle Scholar
- 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.PubMedView ArticleGoogle Scholar
- Eron Jr 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.PubMed CentralPubMedView ArticleGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.