Hepatitis C virus core, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection |
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Authors: | Maarit Sillanpää Krister Melén Päivi Porkka Riku Fagerlund Kaisu Nevalainen Maija Lappalainen Ilkka Julkunen |
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Institution: | 1. Department of Microbiology, University of Iowa, Iowa City, IA, 52242, USA 2. Department of Chemistry, University of Iowa, Iowa City, IA, 52242, USA 3. Department of Microbiology, Immunology and Preventive Medicine, Iowa State University, Ames, IA, 50011, USA 4. Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, 50011, USA 5. Department of Horticulture, Iowa State University, Ames, IA, 50011, USA 8. US Department of Agriculture-Agricultural Research Service, North Central Regional Plant Introduction Station, Ames, IA, 50011, USA 6. Department of Chemistry°, Iowa State University, Ames, IA, 50011, USA 7. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, 50011, USA
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Abstract: | Background Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated. Results Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more polar subfractions. GC/MS analysis of the two most active subfractions identified 3-hydroxy lauric acid as predominant in one fraction and 3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric acid inhibited HIV infectivity without cytotoxicity, suggesting that this modified fatty acid is likely responsible for observed antiviral activity present in that fraction. As production of 3-hydroxy fatty acids by plants remains controversial, H. perforatum seedlings were grown sterilely and evaluated for presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty acids were detected in our chloroform extracts or field-grown material. Conclusion Through bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown Hypericum perforatum has anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents. |
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