Naguib Mahmoud M, Ulrich Reiner, Kasbohm Elisa, Eng Christine L P, Hoffmann Donata, Grund Christian, Beer Martin, Harder Timm C
The Federal Research Institute for Animal Health, Friedrich-Loeffler-Institut, Greifswald Insel-Riems, Germany.
National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Giza, Egypt.
J Virol. 2017 Nov 14;91(23). doi: 10.1128/JVI.01300-17. Print 2017 Dec 1.
The cocirculation of zoonotic highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 and avian influenza virus (AIV) of subtype H9N2 among poultry in Egypt for at least 6 years should render that country a hypothetical hot spot for the emergence of reassortant, phenotypically altered viruses, yet no reassortants have been detected in Egypt. The present investigations proved that reassortants of the Egyptian H5N1 clade 2.2.1.2 virus and H9N2 virus of the G1-B lineage can be generated by coamplification in embryonated chicken eggs. Reassortants were restricted to the H5N1 subtype and acquired between two and all six of the internal segments of the H9N2 virus. Five selected plaque-purified reassortant clones expressed a broad phenotypic spectrum both and Two groups of reassortants were characterized to have retarded growth characteristics compared to the H5N1 parent virus. One clone provoked reduced mortality in inoculated chickens, although the characteristics of a highly pathogenic phenotype were retained. Enhanced zoonotic properties were not predicted for any of these clones, and this prediction was confirmed by ferret inoculation experiments: neither the H5N1 parent virus nor two selected clones induced severe clinical symptoms or were transmitted to sentinel ferrets by contact. While the emergence of reassortants of Egyptian HPAIV of subtype H5N1 with internal gene segments of cocirculating H9N2 viruses is possible in principle, the spread of such viruses is expected to be governed by their fitness to outcompete the parental viruses in the field. The eventual spread of attenuated phenotypes, however, would negatively impact syndrome surveillance on poultry farms and might foster enzootic virus circulation. Despite almost 6 years of the continuous cocirculation of highly pathogenic avian influenza virus H5N1 and avian influenza virus H9N2 in poultry in Egypt, no reassortants of the two subtypes have been reported. Here, the principal compatibility of the two subtypes is shown by forcing the reassortment between copassaged H5N1 und H9N2 viruses in embryonated chicken eggs. The resulting reassortant viruses displayed a wide range of pathogenicity including attenuated phenotypes in chickens, but did not show enhanced zoonotic propensities in the ferret model.
在埃及，H5N1亚型人畜共患高致病性禽流感病毒（HPAIV）和H9N2亚型禽流感病毒（AIV）在禽类中共同传播至少6年，这使该国成为重组的、表型改变病毒出现的假设热点地区，但在埃及尚未检测到重组病毒。目前的研究证明，埃及H5N1进化分支2.2.1.2病毒和G1-B谱系的H9N2病毒的重组病毒可通过在鸡胚中共同扩增产生。重组病毒仅限于H5N1亚型，并获得了H9N2病毒内部片段中的2个至全部6个片段。五个经过噬斑纯化的重组克隆在体外和体内均表现出广泛的表型谱。与H5N1亲本病毒相比，两组重组病毒具有生长特性延迟的特点。一个克隆在接种鸡中引起的死亡率降低，尽管保留了高致病性表型的特征。这些克隆均未预测到增强的人畜共患特性，雪貂接种实验证实了这一预测：H5N1亲本病毒和两个选定的克隆均未引起严重的临床症状，也未通过接触传播给哨兵雪貂。虽然原则上H5N1亚型埃及HPAIV与共同传播的H9N2病毒的内部基因片段发生重组是可能的，但预计此类病毒的传播将取决于它们在野外胜过亲本病毒的适应性。然而，减毒表型的最终传播将对家禽农场的综合征监测产生负面影响，并可能促进动物疫病病毒的循环。尽管高致病性禽流感病毒H5N1和禽流感病毒H9N2在埃及禽类中持续共同传播了近6年，但尚未报道这两个亚型的重组病毒。在此，通过在鸡胚中促使共同传代的H5N1和H9N2病毒之间发生重组，显示了这两个亚型的主要兼容性。产生的重组病毒表现出广泛的致病性，包括鸡中的减毒表型，但在雪貂模型中未显示出增强的人畜共患倾向。
