College of Agriculture & Natural Resources
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Item Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt(MDPI, 2018-03-09) Kim, Shin-HeeHighly pathogenic avian influenza (HPAI) H5N1 viruses are currently endemic in poultry in Egypt. Eradication of the viruses has been unsuccessful due to improper application of vaccine-based control strategies among other preventive measures. The viruses have evolved rapidly with increased bird-to-human transmission efficacy, thus affecting both animal and public health. Subsequent spread of potentially zoonotic low pathogenic avian influenza (LPAI) H9N2 in poultry has also hindered efficient control of avian influenza. The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts. The receptor binding site of HA of Egyptian H9N2 viruses has been shown to contain the Q234L substitution along with a H191 mutation, which can increase human-like receptor specificity. Therefore, co-circulation of H5N1 and H9N2 viruses in poultry farming and live bird markets has increased the risk of human exposure, resulting in complication of the epidemiological situation and raising a concern for potential emergence of a new influenza A virus pandemic. For efficient control of infection and transmission, the efficacy of vaccine and vaccination needs to be improved with a comprehensive control strategy, including enhanced biosecurity, education, surveillance, rapid diagnosis and culling of infected poultry.Item Improved hatchability and efficient protection after in ovo vaccination with live-attenuated H7N2 and H9N2 avian influenza viruses(2011-01-21) Cai, Yibin; Song, Haichen; Ye, Jianqiang; Shao, Hongxia; Padmanabhan, Rangarajan; Sutton, Troy C; Perez, Daniel RMass in ovo vaccination with live attenuated viruses is widely used in the poultry industry to protect against various infectious diseases. The worldwide outbreaks of low pathogenic and highly pathogenic avian influenza highlight the pressing need for the development of similar mass vaccination strategies against avian influenza viruses. We have previously shown that a genetically modified live attenuated avian influenza virus (LAIV) was amenable for in ovo vaccination and provided optimal protection against H5 HPAI viruses. However, in ovo vaccination against other subtypes resulted in poor hatchability and, therefore, seemed impractical. In this study, we modified the H7 and H9 hemagglutinin (HA) proteins by substituting the amino acids at the cleavage site for those found in the H6 HA subtype. We found that with this modification, a single dose in ovo vaccination of 18- day old eggs provided complete protection against homologous challenge with low pathogenic virus in ≥70% of chickens at 2 or 6 weeks post-hatching. Further, inoculation of 19-day old egg embryos with 10 6 EID50 of LAIVs improved hatchability to ≥90% (equivalent to unvaccinated controls) with similar levels of protection. Our findings indicate that the strategy of modifying the HA cleavage site combined with the LAIV backbone could be used for in ovo vaccination against avian influenza. Importantly, with protection conferred as early as 2 weeks post-hatching, with this strategy birds would be protected prior to or at the time of delivery to a farm or commercial operation.Item Molecular markers of interspecies transmission of H2N2 and H9N2 avian influenza A viruses(2008-11-19) Sorrell, Erin Maureen; Perez, Daniel R; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Most avian influenza viruses do not replicate or transmit efficiently in mammals. The events that lead to interspecies transmission and host adaptation are unknown. Part one of this project set out to establish quail as an intermediate host of influenza. Our results indicate that adapting a mallard H2N2 virus in quail leads to expanded host range in chickens. The molecular changes, which occur during the adaptation in quail, are crucial for viral replication and transmission in chickens. Further adaptation of this quail-adapted virus in chickens leads to a 27 amino acid-deletion in the stalk region of the NA, changing the tissue tropism and temperature phenotype of the virus. H9N2 influenza viruses have created in poultry an endemic situation in much of Asia, Europe and the Middle East. This subtype, albeit low pathogenic, carries with it human receptor specificity and the ability to infect humans without prior adaptation. The generation of an influenza pandemic requires interspecies transmission of a novel strain, which can adapt to its new host through either reassortment or point mutations. Given that two previous pandemics were the result of reassortment between low pathogenic avian viruses and human subtypes of that period, and given the endemic situation of avian H9N2 viruses in Eurasia, for part two of this project, we wanted to determine if adaptation of an avian-human H9N2 reassortant in ferrets could support mammalian respiratory droplet transmission. Here we show for the first time that a reassortant virus carrying the HA and NA of an avian H9N2 virus can transmit in respiratory droplets. This is the first report of respiratory droplet transmission of H9N2 influenza, which carries profound implications for pandemic preparedness. The amino acid changes on the HA might identify critical, adaptive mutations necessary for respiratory transmission in subsequent pandemic avian influenza strains. Using reverse genetics we identified key combinations of this adapted reassortant that support respiratory droplet transmission.