Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypogl...Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum （level） Hutch （Celastraceae） is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect （CPE） assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity （CC50 = 46.6μg/mL） and potent CPE inhibition activity, the 50% inhibitory concentration （ICs0） was 6.5 μg/mL, noticeably lower than that of Acyclovir （15.4μg /mL）. Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75% which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% （UL30）, 70.9% （UL39） and 62.6% （US6） respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.展开更多
Most epidemic models for the spread of diseases in contact networks take the assumption of the infected probability of a susceptible agent dependent on its absolute number of infectious neighbours. We introduce a new ...Most epidemic models for the spread of diseases in contact networks take the assumption of the infected probability of a susceptible agent dependent on its absolute number of infectious neighbours. We introduce a new epidemic model in which the infected probability of a susceptible agent in contact networks depends not on its degree but on its exposure level. We find that effective average infection rate ^-λ （i.e., the average number of infections produced by a single contact between infected individuals and susceptible individuals） has an epidemic threshold ^λc = 1, which is related to recovery rate, epidemic mechanisms and topology of contact network. Furthermore, we show the dominating importance of epidemic mechanisms in determining epidemic patterns and discussed the implications of our model for infection control policy.展开更多
Objective To study the mechanism of the cellular proteins involved in the process of replication of hepatitis C virus (HCV) negative-strand RNA.Methods Ultraviolet (UV) cross-linking was used to identify the cellular ...Objective To study the mechanism of the cellular proteins involved in the process of replication of hepatitis C virus (HCV) negative-strand RNA.Methods Ultraviolet (UV) cross-linking was used to identify the cellular proteins that would bind to the 3' -end of HCV negative-strand RNA. Competition experiment was used to confirm the specificity of this binding, in which excess nonhomologous protein and RNA transcripts were used as competitors. The required binding sequence was determined by mapping, then the binding site was predicted through secondary structure analysis.Results A cellular protein of 45 kD (p45) was found to bind specifically to the 3' -end of HCV negative-strand RNA by UV cross-linking, nhomologous proteins and RNA transcripts could not compete out this binding, whereas the unlabeled 3' -end of HCV negative-strand RNA could. Mapping of the protein-binding site suggested that the 3' -end 131-278nt of HCV negative-strand RNA was the possible protein-binding region. Analysis of RNA secondary structure presumed that the potential binding site was located at 194-GAAAGAAC-201.Conclusion The cellular protein p45 could specifically bind to the secondary structure of the 3' -end of HCV intermediate negative-strand RNA, and may play an important role in HCV RNA replication.展开更多
基金The Joint Funds of National Science Foundation of China (U0632010)The State Key Laboratory of Phytochemistry and Plant Resources in West China+1 种基金Chinese Academy of Sciences (O807B11211, O807E21211)"211 grant of MOE"
文摘Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum （level） Hutch （Celastraceae） is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect （CPE） assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity （CC50 = 46.6μg/mL） and potent CPE inhibition activity, the 50% inhibitory concentration （ICs0） was 6.5 μg/mL, noticeably lower than that of Acyclovir （15.4μg /mL）. Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75% which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% （UL30）, 70.9% （UL39） and 62.6% （US6） respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.
基金Supported by the Key Program Projects of the National Natural Science of China under Grant No 70431002, and the National Natural Science Foundation of China under Grant No 10372054.
文摘Most epidemic models for the spread of diseases in contact networks take the assumption of the infected probability of a susceptible agent dependent on its absolute number of infectious neighbours. We introduce a new epidemic model in which the infected probability of a susceptible agent in contact networks depends not on its degree but on its exposure level. We find that effective average infection rate ^-λ （i.e., the average number of infections produced by a single contact between infected individuals and susceptible individuals） has an epidemic threshold ^λc = 1, which is related to recovery rate, epidemic mechanisms and topology of contact network. Furthermore, we show the dominating importance of epidemic mechanisms in determining epidemic patterns and discussed the implications of our model for infection control policy.
基金This work was supported by Scientific Research Grant of Guangdong Province(No.990098,990101).
文摘Objective To study the mechanism of the cellular proteins involved in the process of replication of hepatitis C virus (HCV) negative-strand RNA.Methods Ultraviolet (UV) cross-linking was used to identify the cellular proteins that would bind to the 3' -end of HCV negative-strand RNA. Competition experiment was used to confirm the specificity of this binding, in which excess nonhomologous protein and RNA transcripts were used as competitors. The required binding sequence was determined by mapping, then the binding site was predicted through secondary structure analysis.Results A cellular protein of 45 kD (p45) was found to bind specifically to the 3' -end of HCV negative-strand RNA by UV cross-linking, nhomologous proteins and RNA transcripts could not compete out this binding, whereas the unlabeled 3' -end of HCV negative-strand RNA could. Mapping of the protein-binding site suggested that the 3' -end 131-278nt of HCV negative-strand RNA was the possible protein-binding region. Analysis of RNA secondary structure presumed that the potential binding site was located at 194-GAAAGAAC-201.Conclusion The cellular protein p45 could specifically bind to the secondary structure of the 3' -end of HCV intermediate negative-strand RNA, and may play an important role in HCV RNA replication.
