Preliminary MicroRNA Analysis in Lung Tissue to Identify Potential Therapeutic Targets Against H5N1 Infection

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Abstract

Within the past decade, human infections with the highly pathogenic avian influenza H5N1 have resulted in approximately 60% mortality and increased the need for vaccines and therapeutics. Understanding the molecular events associated with pathology can aid this effort; therefore, this study was conducted to assess microRNA (miRNA) expression in mouse lungs infected with H5N1 A/Vietnam/1203/04. Intranasal administration of 1500 median tissue culture infectious dose of H5N1 promoted differences in the number and expression pattern of miRNA from lung tissue collected at 2, 4, 6, 24, and 96 h post-exposure that mapped to common biological functions. Informatics analysis identified miRNA-specific predicted genes known to be therapeutic drug targets in which Furin was common to all time periods. This study provides insight into the differential miRNA expression with respect to the host-pathogen relationship and identification of potential therapeutic drug targets.

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Highly Pathogenic Avian Influenza (H5N1): Pathways of Exposure at the Animal‐Human Interface, a Systematic Review

Maria D. Van Kerkhove, Elizabeth Mumford, Anthony Mounts … (2011)

Background The threat posed by highly pathogenic avian influenza A H5N1 viruses to humans remains significant, given the continued occurrence of sporadic human cases (499 human cases in 15 countries) with a high case fatality rate (approximately 60%), the endemicity in poultry populations in several countries, and the potential for reassortment with the newly emerging 2009 H1N1 pandemic strain. Therefore, we review risk factors for H5N1 infection in humans. Methods and Findings Several epidemiologic studies have evaluated the risk factors associated with increased risk of H5N1 infection among humans who were exposed to H5N1 viruses. Our review shows that most H5N1 cases are attributed to exposure to sick poultry. Most cases are sporadic, while occasional limited human-to-human transmission occurs. The most commonly identified factors associated with H5N1 virus infection included exposure through contact with infected blood or bodily fluids of infected poultry via food preparation practices; touching and caring for infected poultry; consuming uncooked poultry products; exposure to H5N1 via swimming or bathing in potentially virus laden ponds; and exposure to H5N1 at live bird markets. Conclusions Research has demonstrated that despite frequent and widespread contact with poultry, transmission of the H5N1 virus from poultry to humans is rare. Available research has identified several risk factors that may be associated with infection including close direct contact with poultry and transmission via the environment. However, several important data gaps remain that limit our understanding of the epidemiology of H5N1 in humans. Although infection in humans with H5N1 remains rare, human cases continue to be reported and H5N1 is now considered endemic among poultry in parts of Asia and in Egypt, providing opportunities for additional human infections and for the acquisition of virus mutations that may lead to more efficient spread among humans and other mammalian species. Collaboration between human and animal health sectors for surveillance, case investigation, virus sharing, and risk assessment is essential to monitor for potential changes in circulating H5N1 viruses and in the epidemiology of H5N1 in order to provide the best possible chance for effective mitigation of the impact of H5N1 in both poultry and humans. Disclaimer The opinions expressed in this article are those of the authors and do not necessarily reflect those of the institutions or organizations with which they are affiliated.

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Environmental persistence of a highly pathogenic avian influenza (H5N1) virus.

Daniel J Chappie, Y. Choi, Frederic J. Kaye … (2010)

Human cases of disease caused by highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype are rare, yet characterized with a mortality rate of approximately 60%. Tests were conducted to determine the environmental persistence of an HPAI (H5N1) virus on four materials (glass, wood, galvanized metal, and topsoil) that could act as fomites or harbor the virus. Test coupons were inoculated with the virus and exposed to one of five environmental conditions that included changes in temperature, relative humidity, and simulated sunlight. At time periods up to 13 days, the virus was extracted from each coupon, and quantified via cytopathic effects on Madin-Darby canine kidney cells. The virus was most persistent under the low temperature condition, with less than 1 log reduction on glass and steel after 13 days at low relative humidity. Thus, at these conditions, the virus would be expected to persist appreciably beyond 13 days.

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Pandemic H5N1 influenza vaccine development: an update.

Wendy Keitel, H Sahly (2008)

The spread and evolution of highly pathogenic influenza A/H5N1 viruses in birds worldwide, and the associated human fatalities, have raised concern about an imminent influenza pandemic. Studies evaluating the safety and immunogenicity of traditional (egg-grown, subvirion and whole virus) vaccines and alternative vaccine approaches (recombinant, live-attenuated and adjuvanted vaccines) have been performed. Results show that, using unadjuvanted subvirion vaccines, at least two vaccine doses containing high dosages of influenza virus hemagglutinin are needed to elicit a titer of antibody that has been associated with protection in vaccinated subjects. High antigen-dosage requirements may be reduced and immunogenicity improved with the use of whole virus vaccines or adjuvants, such as MF59 and GlaxoSmithKline proprietary adjuvant. There is a suggestion that prepandemic priming against drifted H5N1 variants is possible; however, additional data are needed. Newer approaches using live-attenuated, DNA vaccines and conserved epitopes are currently under development.