Earl Brown

Publications (79) View all

• Article: Low-pathogenic avian influenza virus A/turkey/Ontario/6213/1966 (H5N1) is the progenitor of highly pathogenic A/turkey/Ontario/7732/1966 (H5N9).

  Jihui Ping, Mohammed Selman, Shaun Tyler, Nicole Forbes, Liya Keleta, Earl G Brown
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  ABSTRACT: The first confirmed outbreak of highly pathogenic avian influenza (HPAI) virus infections in North America was caused by A/turkey/Ontario/7732/1966 (H5N9); however, the phylogeny of this virus is largely unknown. This study performed genomic sequence analysis of 11 avian influenza isolates from 1956 to 1979 for comparison with A/turkey/Ontario/7732/1966 (H5N9). Phylogenetic and genetic analyses included these viruses in combination with all known full-genome sequences of avian viruses isolated before 1981. It was shown that a low-pathogenic avian influenza virus, A/turkey/Ontario/6213/1966 (H5N1), that had been isolated 3 months previously, was the closest known genetic relative with six genome segments of common lineage encoding the polymerase subunits PB2, PB1 and PA, nucleoprotein (NP), haemagglutinin (HA) and non-structural (NS) proteins. The lineages of these genome segments included reassortment with other North American turkey viruses that were all rooted in North American wild waterfowl with the HA gene originating from the H5N2 serotype. The phylogenies demonstrated adaptation from North American wild birds to turkeys with the possible involvement of domestic waterfowl. The turkey isolate, A/turkey/Wisconsin/1968 (H5N9), was the second most closely related poultry isolate to A/turkey/Ontario/7732/1966 (H5N9), possessing five common lineage genome segments (PB2, PB1, PA, HA and neuraminidase). The A/turkey/Ontario/6213/1966 (H5N1) virus was more virulent than A/turkey/Wisconsin/68 (H5N9) for chicken embryos and mice, indicating a greater biological similarity to A/turkey/Ontario/7732/1966 (H5N9). Thus, A/turkey/Ontario/6213/1966 (H5N1) was identified as the closest known ancestral relative of HPAI A/turkey/Ontario/7732/1966 (H5N9), which will serve as a useful reference virus for characterizing the early genetic and biological properties associated with the emergence of pathogenic avian influenza strains.
  Journal of General Virology 05/2012; 93(Pt 8):1649-57. · 3.36 Impact Factor
• Article: Genetic analysis of H3 subtype influenza viruses isolated from domestic ducks in northern China during 2004-2005.

  Juan Pu, Qin-Fang Liu, Ying-Ju Xia, Yu-Lei Fan, Earl G Brown, Fu-Lin Tian, Jin-Hua Liu
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  ABSTRACT: The broad distribution and prevalence of H3 subtype influenza viruses in avian and mammalian hosts constitutes a global threat to both human and veterinary health. In this present study, six H3N8 influenza viruses isolated from domestic ducks during 2004-2005 in northern China were genetically and phylogenetically characterized. Sequence analysis showed that HA, NA, and M genes of all the six H3N8 isolates had a close relationship with those of Equine/Jilin/1/89 (H3N8) virus, which once caused outbreak in equine populations in northern China. The PB2 and PA genes of the viruses possessed the highest similarities with highly pathogenic avian H5N1 influenza viruses currently circulating in this region. These findings emphasize the importance of avian influenza virus surveillance in this region for understanding the genesis and emergency of novel reassortants with pandemic potential.
  Virus Genes 01/2009; 38(1):136-42. · 1.85 Impact Factor
• Chapter: Additive Inhibition of H1N1 and H3N2 Influenza Viruses by Aurintricarboxylic Acid With Amantadine

  Anathea S Flaman, Homan Albaghdadi, Jeff McClintock, Todd Cutts, Anwar M Hashem, Matt LeBrun, John Austin, Earl Brown, Runtao He, Xuguang Li
  01/2008: pages 478-479; , ISBN: 978-1-901-769-15-6
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  Available from: Earl Brown

  Article: Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross-Protective Antibodies that Target the Hemagglutinin Stem.

  C A Thomson, Y Wang, L M Jackson, M Olson, W Wang, A Liavonchanka, L Keleta, V Silva, S Diederich, R B Jones, J Gubbay, J Pasick, M Petric, François Jean, V G Allen, E G Brown, J M Rini, J W Schrader
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  ABSTRACT: Most monoclonal antibodies (mAbs) generated from humans infected or vaccinated with the 2009 pandemic H1N1 (pdmH1N1) influenza virus targeted the hemagglutinin (HA) stem. These anti-HA stem mAbs mostly used IGHV1-69 and bound readily to epitopes on the conventional seasonal influenza and pdmH1N1 vaccines. The anti-HA stem mAbs neutralized pdmH1N1, seasonal influenza H1N1 and avian H5N1 influenza viruses by inhibiting HA-mediated fusion of membranes and protected against and treated heterologous lethal infections in mice with H5N1 influenza virus. This demonstrated that therapeutic mAbs could be generated a few months after the new virus emerged. Human immunization with the pdmH1N1 vaccine induced circulating antibodies that when passively transferred, protected mice from lethal, heterologous H5N1 influenza infections. We observed that the dominant heterosubtypic antibody response against the HA stem correlated with the relative absence of memory B cells against the HA head of pdmH1N1, thus enabling the rare heterosubtypic memory B cells induced by seasonal influenza and specific for conserved sites on the HA stem to compete for T-cell help. These results support the notion that broadly protective antibodies against influenza would be induced by successive vaccination with conventional influenza vaccines based on subtypes of HA in viruses not circulating in humans.
  Frontiers in immunology. 01/2012; 3:87.
• Article: Critical negative regulation of type 1 T cell immunity and immunopathology by signaling adaptor DAP12 during intracellular infection.

  Maziar Divangahi, Tony Yang, Kapilan Kugathasan, Sarah McCormick, Shunsuke Takenaka, Gordon Gaschler, Ali Ashkar, Martin Stampfli, Jack Gauldie, Jonathan Bramson, Toshiyuki Takai, Earl Brown, Wayne M Yokoyama, Naoko Aoki, Zhou Xing
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  ABSTRACT: Transmembrane signaling adaptor DAP12 has increasingly been recognized for its important role in innate responses. However, its role in the regulation of antimicrobial T cell responses has remained unknown. In our current study, we have examined host defense, T cell responses, and tissue immunopathology in models of intracellular infection established in wild-type and DAP12-deficient mice. During mycobacterial infection, lack of DAP12 leads to pronounced proinflammatory and Th1 cytokine responses, overactivation of Ag-specific CD4 and CD8 T cells of type 1 phenotype, and heightened immunopathology both in the lung and lymphoid organs. DAP12-deficient airway APC display enhanced NF-kappaB activation and cytokine responses upon TLR stimulation or mycobacterial infection in vitro. Of importance, adoptive transfer of Ag-loaded DAP12-deficient APC alone could lead to overactivation of transferred transgenic or endogenous wild-type T cells in vivo. We have further found that the immune regulatory role by DAP12 is not restricted only to intracellular bacterial infection, since lack of this molecule also leads to uncontrolled type 1 T cell activation and severe immunopathology and tissue injury during intracellular viral infection. Our study thus identifies DAP12 as an important novel immune regulatory molecule that acts, via APC, to control the level of antimicrobial type 1 T cell activation and immunopathology.
  The Journal of Immunology 10/2007; 179(6):4015-26. · 5.79 Impact Factor