Immunomodulatory and anti-viral effects of statins in influenza H5N1 virus infection of human alveolar epithelial cells and peripheral blood–derived macrophages

Poster Session: Novel TherapeuticsBackground: Highly pathogenic avian influenza (HPAI) H5N1 virus panzootic in poultry continues to spread. It causes zoonotic human disease with a high (> 60%) fatality rate and continues to pose a pandemic threat. Based on clinical, animal, and in vitro cell studies, we and others have suggested that differences in viral replication competence, tissue tropism, and cytokine dysregulation between H5N1 and low pathogenic viruses may contribute to disease pathogenesis. Statins as HMG-CoA inhibitors act to reduce cholesterol and have been demonstrated to have anti-inflammatory and immune-modulatory activities. However, there is controversy about the benefits of statin use on influenza infection in mice and humans. In this study, we aimed to evaluate the effects of statin treatment in influenza infection using physiologically relevant in vitro models—human alveolar epithelial cells (AECs) and peripheral blood–derived macrophages (PBDMs). Materials and Methods: Primary human AECs and PBDMs were infected with HPAI H5N1 (A/HK/483/97) and seasonal H1N1 (A/HK/54/98) viruses in the presence or absence of statin (simvastatin and sevastatin) treatment. Virus replication was monitored by measuring infectious viral particles in cell culture supernatants using TCID50. Immuno-modulatory effects of statins were examined by measuring the mRNA and protein expression of cytokines and chemokines using qPCR and ELISA. In order to understand the intervention of statins and influenza infection, the gene expression profile of selected members of the sterol-biosynthesis pathway in influenza virus–infected AECs and PBDMs were also monitored. The responses of a variety of cytokine treatments on the genes of the sterol-biosynthesis pathway were investigated in AECs. Furthermore, the intracellular free cholesterol level was also examined by enzymatic assay in AECs infected with influenza virus. Results: We demonstrated that both simvastatin and mevastatin exhibited a dose-dependent inhibition of influenza virus replication for both HPAI H5N1 and seasonal H1N1 viruses in human AECs and PBDMs. The observed inhibitory effect of simvastatin and mevastatin occurred below the non-specific toxic effects to cells, which were measured by MTT assay. Treatment of simvastatin and mevastatin significantly suppressed H5N1 virus–induced pro-inflammatory cytokines such as TNF-α in PBDMs and chemokines, including IP-10 and MCP-1 secretion in both AECs and PBDMs at 24 hours post-infection. We further showed that human AECs and PBDMs infected with both HPAI H5N1 and seasonal H1N1 viruses had significant down-regulation of sterol pathway gene expression at 24 hours post-infection. AECs and PBDMs treated with IFN-γ or IFN-β but not IL-1β, TNF, or IL-6, showed down-regulation of sterol pathway gene expression. In addition, we found that the free cholesterol level was significantly reduced at 24 and 48 h post-H5N1 virus infection in AECs and in IFN-β–treated AECs. These results further support a specific modulation of the sterol metabolic pathway upon influenza virus infection. Conclusions: Taken together, the controversy about the beneficial effects of statin use in influenza infection and our data suggest that statins possess both the antiviral and immune-regulatory effects in H5N1-infected in vitro cell models. We also demonstrated a highly specific response of AECs and PBDMs through a coordinated negative regulation of multiple sterol pathway members upon influenza virus infection or treatment of interferon. Identification of a reduction in sterol pathway gene expression and cholesterol levels with IFN treatment in human AECs offers new insights on the host-mediated antiviral responses through the sterol metabolism pathway and opens new therapeutic options for human influenza disease.published_or_final_versio

Engineering education opportunities, perceptions and career choice of secondary school students in Hong Kong SAR, China

Session Title: Engineering Education and Comparative Studies at Universities throughout Asia, Far East: AC 2012-5321This paper presents an investigation into engineering education opportunities and engagement among secondary school students in Hong Kong SAR, China (HK). We adapted and validated an international questionnaire and executed it in HK secondary schools. The questionnaire is designed to identify pedagogy, students' perception, and experience (formal and informal) of engineering education, and measure their effects on students' career choice in engineering. We investigate how do factors like age, gender, family background (local versus new immigrants), subjects taken at school, and perceptions of the engineering profession affect their career choice in engineering. Identifying factors affecting young people's career choice in engineering is interesting as HK is in an early post-industrial position. Such study can provide an excellent comparative example to contrast between post-industrial societies such as the United States and industrializing societies such as other cities in the mainland China. © 2012 American Society for Engineering Education.postprin

How Integrative Intervention Alleviates Insomnia-Related Stresses: A Qualitative Study

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Understanding the preferred role in infertility treatment decision making among Chinese infertile women in Hong Kong

Session 38: Managing patient expectations: no. O-140This free journal suppl. entitled: Abstract book of the 31st ESHRE Annual Meeting, Lisbon, Portugal, 14–17 June 2015STUDY QUESTION: What are the treatment decision making preferences in Chinese women undergoing fertility treatments in Hong Kong? ...postprin

Semaphorin3A, associated with perineuronal nets, regulates the development of the maturation of the central vestibular circuitry

Poster Presentation - Theme 5: NeuroscienceDuring the formative period of neural circuits, perineuronal nets (PN) are established to restrict plasticity of the circuit. The role of PN in vestibular plasticity can be tested by studying the emergence of negative geotaxis with postnatal maturation of the vestibular circuitry for gravity detection. Using rats as model, we observed that negative geotaxis was mature by postnatal day (P) 9, in correlation with consolidation of PN around GABAergic neurons …postprin

Perineuronal chondroitin sulfates and semaphorin 3A regulate postnatal maturation of the vestibular circuit for gravity detection

Conference Theme: The Extracellular Matrix NichePoster Presentation: abstract no. P30Perineuronal chondroitin sulfate proteoglycan networks are implicated in restricting plasticity of the mature CNS. Less is known of the impact of ligands associated with the perineuronal network (PN) in the formative period of neural circuits. The emergence of negative geotaxis with postnatal maturation of the vestibular circuitry for gravity detection offers a behavioral readout in tests for roles of the PN and associated ligands in vestibular plasticity. Using postnatal rats as model, we found that negative geotaxis was mature by postnatal day (P) 9, in correlation with ...postprin

A randomised controlled trial to compare immunogenicity between intramuscular and intradermal trivalent influenza vaccination in nursing home older adults

BACKGROUND: Immunosenescence in older adults contributes to unsatisfactory immunogenicity towards influenza vaccine. Intradermal (ID) administration of influenza vaccine has been suggested to improve immunogenicity but there is no study regarding the immunogenicity of ID influenza vaccination in nursing home older adults ...postprin

Environmental factors and mortality risks associated influenza

BACKGROUND AND AIMS: The subtropical and tropical regions exhibit a distinct seasonality of influenza incidence from the temperate regions, and the mechanism behind it remains unclear. Environmental factors have been related to the transmission and survival of influenza viruses but no studies have ever explored the role of environmental factors on regulating severity of influenza infection. METHODS: We applied a Poisson regression model to the mortality data of two Asian metropolitan cities located at the subtropical zone, Guangzhou and Hong Kong. Interaction between …postprin

Cultural fairness of the Digit Vigilance Test

This study was designed to examine the cultural fairness of the Digit Vigilance Test by comparing performance on the test between Chinese and American participants. Thirty-five Chinese undergraduates, 12 male and 23 female, were recruited as participants. Their scores on the test, specifically the time and error scores, were compared with the published American norms. The findings indicated equivalent performance of the two samples on the test, suggesting the cultural fairness of the Digit Vigilance Test. Nevertheless, generalization of the present findings to other Chinese populations should take into consideration the unique characteristics of the sample in this study.published_or_final_versio