Simulundu Edgar, Nao Naganori, Yabe John, Muto Nilton A, Sithebe Thami, Sawa Hirofumi, Manzoor Rashid, Kajihara Masahiro, Muramatsu Mieko, Ishii Akihiro, Ogawa Hirohito, Mweene Aaron S, Takada Ayato
Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Kita-20, Nishi-10, Kita-ku, Sapporo, 001-0020, Japan.
Arch Virol. 2014 Oct;159(10):2633-40. doi: 10.1007/s00705-014-2124-1. Epub 2014 May 27.
Whilst remarkable progress in elucidating the mechanisms governing interspecies transmission and pathogenicity of highly pathogenic avian influenza viruses (AIVs) has been made, similar studies focusing on low-pathogenic AIVs isolated from the wild waterfowl reservoir are limited. We previously reported that two AIV strains (subtypes H6N2 and H3N8) isolated from wild waterfowl in Zambia harbored some amino acid residues preferentially associated with human influenza virus proteins (so-called human signatures) and replicated better in the lungs of infected mice and caused more morbidity than a strain lacking such residues. To further substantiate these observations, we infected chickens and mice intranasally with AIV strains of various subtypes (H3N6, H3N8, H4N6, H6N2, H9N1 and H11N9) isolated from wild waterfowl in Zambia. Although some strains induced seroconversion, all of the tested strains replicated poorly and were nonpathogenic for chickens. In contrast, most of the strains having human signatures replicated well in the lungs of mice, and one of these strains caused severe illness in mice and induced lung injury that was characterized by a severe accumulation of polymorphonuclear leukocytes. These results suggest that some strains tested in this study may have the potential to infect mammalian hosts directly without adaptation, which might possibly be associated with the possession of human signature residues. Close monitoring and evaluation of host-associated signatures may help to elucidate the prevalence and emergence of AIVs with potential for causing zoonotic infections.
尽管在阐明高致病性禽流感病毒（AIV）种间传播和致病性的机制方面已取得显著进展，但针对从野生水禽宿主分离出的低致病性AIV的类似研究却很有限。我们之前报道过，从赞比亚野生水禽中分离出的两种AIV毒株（H6N2和H3N8亚型）含有一些优先与人流感病毒蛋白相关的氨基酸残基（所谓的人类特征），并且在感染小鼠的肺部复制得更好，与缺乏这些残基的毒株相比，导致的发病率更高。为了进一步证实这些观察结果，我们用从赞比亚野生水禽中分离出的各种亚型（H3N6、H3N8、H4N6、H6N2、H9N1和H11N9）的AIV毒株经鼻内感染鸡和小鼠。尽管一些毒株诱导了血清转化，但所有测试毒株的复制能力都很差，并且对鸡无致病性。相比之下，大多数具有人类特征的毒株在小鼠肺部复制良好，其中一种毒株在小鼠中引起严重疾病，并导致以多形核白细胞严重聚集为特征的肺损伤。这些结果表明，本研究中测试的一些毒株可能有直接感染哺乳动物宿主而无需适应的潜力，这可能与拥有人类特征残基有关。对宿主相关特征进行密切监测和评估可能有助于阐明具有人畜共患感染潜力的AIV的流行情况和出现情况。
