Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

Host defenses against viral infections depend on a complex interplay of innate (nonspecific) and adaptive (specific) components. In the early stages of infection, innate mechanisms represent the main line of host defense, acting to limit the spread of virus in host tissues prior to the induction of the adaptive immune response. Serum and lung fluids contain a range of lectins capable of recognizing and destroying influenza A viruses (IAV). Herein, we review the mechanisms by which soluble endogenous lectins mediate anti-IAV activity, including their role in modulating IAV-induced inflammation and disease and their potential as prophylactic and/or therapeutic treatments during severe IAV-induced disease

Prevention and Treatment of Influenza with Hyperimmune Bovine Colostrum Antibody

Background: Despite the availability of specific vaccines and antiviral drugs, influenza continues to impose a heavy toll on human health worldwide. Passive transfer of specific antibody (Ab) may provide a useful means of preventing or treating disease in unvaccinated individuals or those failing to adequately seroconvert, especially now that resistance to antiviral drugs is on the rise. However, preparation of appropriate Ab in large scale, quickly and on a yearly basis is viewed as a significant logistical hurdle for this approach to control seasonal influenza. Methodology/Principal Findings: In this study, bovine colostrum, which contains approximately 500 g of IgG per milking per animal, has been investigated as a source of polyclonal antibody for delivery to the respiratory tract. IgG and F(ab’)2 were purified from the hyperimmune colostrum of cows vaccinated with influenza A/Puerto Rico/8/34 (PR8) vaccine and were shown to have high hemagglutination-inhibitory and virus-neutralizing titers. In BALB/c mice, a single administration of either IgG or F(ab’)2 could prevent the establishment of infection with a sublethal dose of PR8 virus when given as early as 7 days prior to exposure to virus. Pre-treated mice also survived an otherwise lethal dose of virus, the IgG- but not the F(ab’)2-treated mice showing no weight loss. Successful reduction of established infection with this highly virulent virus was also observed with a single treatment 24 hr after virus exposure. Conclusions/Significance: These data suggest that a novel and commercially-scalable technique for preparing Ab fro

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Distinct DNA methylation epigenotypes in bladder cancer from different Chinese sub-populations and its implication in cancer detection using voided urine

<p>Abstract</p> <p>Background</p> <p>Bladder cancer is the sixth most common cancer in the world and the incidence is particularly high in southwestern Taiwan. Previous studies have identified several tumor-related genes that are hypermethylated in bladder cancer; however the DNA methylation profile of bladder cancer in Taiwan is not fully understood.</p> <p>Methods</p> <p>In this study, we compared the DNA methylation profile of multiple tumor suppressor genes (<it>APC</it>, <it>DAPK</it>, <it>E-cadherin</it>, <it>hMLH1</it>, <it>IRF8</it>, <it>p14</it>, <it>p15</it>, <it>RASSF1A</it>, <it>SFRP1 </it>and <it>SOCS-1</it>) in bladder cancer patients from different Chinese sub-populations including Taiwan (104 cases), Hong Kong (82 cases) and China (24 cases) by MSP. Two normal human urothelium were also included as control. To investigate the diagnostic potential of using DNA methylation in non-invasive detection of bladder cancer, degree of methylation of <it>DAPK</it>, <it>IRF8</it>, <it>p14</it>, <it>RASSF1A </it>and <it>SFRP1 </it>was also accessed by quantitative MSP in urine samples from thirty bladder cancer patients and nineteen non-cancer controls.</p> <p>Results</p> <p>There were distinct DNA methylation epigenotypes among the different sub-populations. Further, samples from Taiwan and China demonstrated a bimodal distribution suggesting that CpG island methylator phentotype (CIMP) is presented in bladder cancer. Moreover, the number of methylated genes in samples from Taiwan and Hong Kong were significantly correlated with histological grade (P < 0.01) and pathological stage (P < 0.01). Regarding the samples from Taiwan, methylation of <it>SFRP1</it>, <it>IRF8</it>, <it>APC </it>and <it>RASSF1A </it>were significantly associated with increased tumor grade, stage. Methylation of <it>RASSF1A </it>was associated with tumor recurrence. Patients with methylation of <it>APC </it>or <it>RASSF1A </it>were also significantly associated with shorter recurrence-free survival. For methylation detection in voided urine samples of cancer patients, the sensitivity and specificity of using any of the methylated genes (<it>IRF8</it>, <it>p14 </it>or <it>sFRP1</it>) by qMSP was 86.7% and 94.7%.</p> <p>Conclusions</p> <p>Our results indicate that there are distinct methylation epigenotypes among different Chinese sub-populations. These profiles demonstrate gradual increases with cancer progression. Finally, detection of gene methylation in voided urine with these distinct DNA methylation markers is more sensitive than urine cytology.</p

Identification and characterization of C-type lectin receptors for respiratory viruses

© 2015 Dr. Wy Ching NgStudies described in this thesis have characterized interactions between respiratory viruses and different C-type lectin receptors. A transfection-based approach was used to express mannose- and galactose-specific C-type lectin receptors and to examine their ability to promote attachment, entry and infection of target cells by influenza A viruses. In addition, we investigated the ability of C-type lectin receptors to promote infection by other respiratory viruses, including mumps virus, Newcastle disease virus, respiratory syncytial virus and parainfluenza virus type-3

Regulation of Proinflammatory Cytokine by Vitmain B2 in Influenza A/H5N1 Virus Infected Human Alveolar Epithelial Cells and Macrophages

Thematic Poster Session: B65 Host-Pathogen Interactions: abstract no. P1254Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poutlry and continues to transmit zoonotically to humans posing a pandemic threat. In preparation for next pandemic, governments all over the world have stockpiled oseltamivir and other antivirals. However, in case of a pandemic, time will be required before a safe and reliable vaccine becomes available. Thus there is a urgent need for adjunctive therapies that may help modulate the severity of the disease. Human H5N1 disease causes unusual disease severity and high mortality, and clinical syndromes have been previously suggested to associate with cytokine dysregulation. Vitamin B2 was shown previously to lowers the serum levels of cytokines and chemokines and improves survival rate in bacterial sepsis models in rodents. This result suggests vitamin B2, could be a promising alternative strategy for the treatment of severe human influenza diseases by modulating the adverse innate immune responses. In this study, we infected the primary human alveolar epithelial cells and peripheral blood derived macrophage with influenza A viruses (H5N1 and H1N1) with or without vitamin B2 treatment and to detemine the mRNA and protein expression of proinflammatory cytokine and chemokine by real-time quantitative RT-PCR and ELISA respectively. Our studies have shown that vitamin B2 is effective in suppressing the hyper induction of cytokine and chemokine (TNF-alpha, IP10, RANTES) upon influenza H5N1 virus infection in alveolar epithelial cells and macrophages in vitro. We hypothese vitamin B2 can be a potential candidate to alleviate the pathology of human H5N1 disease by modulating the host innate immune responses. Understanding the host interaction with influenza virus and the role of vitamin B2 as immunomodulatory agents in human H5N1 disease can provide important insight into the mechanism of pathogenesis and to identify allternative therapy for treatment of avian influenza H5N1 disease

Half-lives of intranasally-delivered bovine IgG in the nose, lungs and serum.

<p>The bovine anti-PR8 IgG preparation (1 mg) was administered in a volume of 50 µl by the i.n. route to anesthetized mice. At 1, 12, 24 and 36 hr post-administration, mice were killed and bovine IgG was detected by capture ELISA in nasal turbinate and lung homogenates and in sera. The total amount of Ab was determined by reference to a standard curve. Linear regression analysis was used to calculate the half-lives of bovine IgG in the different sites. The data are representative of two experiments.</p

Virus loads are reduced but by a lesser extent if Ab treatment is delayed.

<p>BALB/c mice were infected with 50 pfu of PR8 virus in 50 µl via the TRT route under penthrane anaesthesia. Two days post-infection, mice were treated with 1 mg of the Ab preparations or PBS via the TRT route. Five days post-infection, mice were killed and lungs were collected in 1 ml media. Viral titres were determined by plaque assay on MDCK cell monolayers. The experiment was performed once with 5 mice per group, the organs assayed in quadruplicate and titers averaged to provide a value for that animal. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference between the indicated groups.</p

Virus load reduction is not enhanced by a second dosing with Ab.

<p>BALB/c mice were given 500 pfu of PR8 virus in 10 µl by the intranasal route to establish a localised URT infection. One and 3 days post-infection, mice were treated with 200 µg of each Ab preparation or PBS via the URT route. Five days post-infection, mice were killed and nasal turbinates were collected in 1 mL media. Viral titers were determined by plaque assay on MDCK cell monolayers. The experiment was performed once with 4 mice per group, the organs assayed in quadruplicate and titers averaged to provide a value for that animal. Each symbol represents an individual mouse and the line represents the mean of each group. Brackets with an asterisk indicate a statistically significant difference between the indicated groups.</p