Two models for changes of EV71 immunity in infants and young children.

Human enterovirus 71 (EV71) has been associated with outbreaks of hand-foot-and-mouth disease (HFMD) in China. Susceptibility to EV71 is associated with age, but few studies have been accomplished to measure such a relationship. A better understanding of the connection between susceptibility and age is necessary to develop strategies for control of HFMD. In 2010, a survey of an epidemic of EV71 was conducted in a northern city of Jiangsu Province in China. Samples were tested serologically to identify the EV71 neutralizing antibody. Two different mathematical models have now been employed to describe how this antibody varied with age, and parameters in the model were estimated from survey data. Both models depicted the variations in EV71-neutralizing antibody. Seroprevalence was high for neonates but decreased to near zero at 5 months of age. Subsequently, the EV71 antibody levels increased and then remained stable after about 36 months. For models 1 and 2, values for the coefficient of determination (R(2)) were 0.9458 and 0.9576, and values for root mean square error (RMSE) were 0.0755 and 0.0752, respectively. Model 2, formulated from the characteristics of development of the immune system, was more reliable than model 1, formulated from survey data, because the impact of the survey on the structure of the model was removed. Moreover, model 2 provided the possibility to define the parameters in a biological sense.

Elucidating the host-pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling.

Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host-pathogen interaction between human colorectal cells and EV71.

Curcumin inhibits the replication of enterovirus 71 in vitro.

Human enterovirus 71 (EV71) is the main causative pathogen of hand, foot, and mouth disease (HFMD) in children. The epidemic of HFMD has been a public health problem in Asia-Pacific region for decades, and no vaccine and effective antiviral medicine are available. Curcumin has been used as a traditional medicine for centuries to treat a diversity of disorders including viral infections. In this study, we demonstrated that curcumin showed potent antiviral effect again EV71. In Vero cells infected with EV71, the addition of curcumin significantly suppressed the synthesis of viral RNA, the expression of viral protein, and the overall production of viral progeny. Similar with the previous reports, curcumin reduced the production of ROS induced by viral infection. However, the antioxidant property of curcumin did not contribute to its antiviral activity, since N-acetyl-l-cysteine, the potent antioxidant failed to suppress viral replication. This study also showed that extracellular signal-regulated kinase (ERK) was activated by either viral infection or curcumin treatment, but the activated ERK did not interfere with the antiviral effect of curcumin, indicating ERK is not involved in the antiviral mechanism of curcumin. Unlike the previous reports that curcumin inhibited protein degradation through ubiquitin-proteasome system (UPS), we found that curcumin had no impact on UPS in control cells. However, curcumin did reduce the activity of proteasomes which was increased by viral infection. In addition, the accumulation of the short-lived proteins, p53 and p21, was increased by the treatment of curcumin in EV71-infected cells. We further probed the antiviral mechanism of curcumin by examining the expression of GBF1 and PI4KB, both of which are required for the formation of viral replication complex. We found that curcumin significantly reduced the level of both proteins. Moreover, the decreased expression of either GBF1 or PI4KB by the application of siRNAs was sufficient to suppress viral replication. We also demonstrated that curcumin showed anti-apoptotic activity at the early stage of viral infection. The results of this study provide solid evidence that curcumin has potent anti-EV71 activity. Whether or not the down-regulated GBF1 and PI4KB by curcumin contribute to its antiviral effect needs further studies.