Are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza A reassortant viruses?
Are there alternative avian influenza viruses for generation of stable attenuated avian-human influenza A reassortant viruses?
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DOI：
10.1016/0168-1702(95)00082-8
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发表时间：
1995-12-01
期刊：
影响因子：
5
通讯作者：
Murphy, BR
中科院分区：
文献类型：
--
作者：
Subbarao, K;Webster, RG;Murphy, BR
本研究评价了海鸥甲型流感病毒作为减毒基因的供体，用于生产活的减毒甲型流感H1N1和H3 N2禽-人（ah）抵抗病毒，用作疫苗预防人类甲型流感病毒引起的疾病。先前评价的鸭甲型流感病毒被放弃作为减毒禽流感病毒基因的供体，因为对源自鸭病毒的H1N1和H3 N2抗病毒疫苗的临床评价证明了H1N1抗病毒剂对血清阴性婴儿和幼儿的残留毒力。海鸥流感病毒A占据一个独立的生态位，很少从海鸥以外的物种分离。本研究使用三种不同的海鸥型流感病毒和三种人型流感病毒评价了使用海鸥型流感病毒作为抗原病毒内部基因片段供体的可能性。容易产生具有所需6-2基因型（六个内部禽流感病毒基因和两个人流感病毒表面糖蛋白基因）的海鸥-人H3 N2抗流感A病毒，并且发现其对松鼠猴和黑猩猩减毒。然而，难以产生具有海鸥和人甲型流感H1N1基因的重组病毒，并且尽管反复尝试，仍没有分离出具有所需基因型的六种海鸥病毒基因与人甲型流感H1和N1基因的重组病毒。海鸥PB 2、NP和NS基因不存在于所产生的任何海鸥-人H1N1抑制剂中。这三个基因片段的代表性不足表明，携带这三个基因片段中的一个或多个的回复体可能具有降低的活力，这表明其基因产物中的功能不相容性。在产生6-2海鸥-人H1N1抗病毒中遇到的困难足以得出结论，所测试的海鸥甲型流感病毒不能用作减毒人甲型流感病毒的六组内部基因的供体。这项研究还确定了流感病毒的基因片段，似乎是不兼容的产生reflectants。阐明这种限制的分子基础可能提供有关病毒体组装或包装中涉及的基因间相互作用的信息。
The present study evaluated gull influenza A viruses as donors of attenuating genes for the production of live, attenuated influenza A H1N1 and H3N2 avian-human (ah) reassortant viruses for use as vaccines to prevent disease due to influenza A viruses in humans. The previously evaluated duck influenza A viruses were abandoned as donors of attenuating avian influenza virus genes because clinical evaluation of H1N1 and H3N2 ah reassortant virus vaccines derived from duck viruses documented residual virulence of H1N1 reassortants for seronegative infants and young children. Gull influenza A viruses occupy an independent ecologic niche and are rarely isolated from species other than gulls. The possibility of using gull influenza A viruses as donors of internal gene segments in ah reassortant viruses was evaluated in the present study using three different gull viruses and three human influenza A viruses. Gull-human H3N2 reassortant influenza A viruses with the desired 6-2 genotype (six internal avian influenza virus genes and the two human influenza virus surface glycoprotein genes) were readily generated and were found to be attenuated for squirrel monkeys and chimpanzees. However, ah reassortant viruses with gull and human influenza A H1N1 genes were difficult to generate, and reassortants that had the desired genotype of six gull virus genes with human influenza A H1 and N1 genes were not isolated despite repeated attempts. The gull PB2, NP and NS genes were not present in any of the gull-human H1N1 reassortants generated. The under-representation of these three gene segments suggests that reassortants bearing one or more of these three gene segments might have reduced viability indicative of a functional incompatibility in their gene products. The difficulties encountered in the generation of a 6-2 gull-human H1N1 reassortant virus are sufficient to conclude that the gull influenza A viruses tested would not be useful as donors of sets of six internal genes to attenuate human influenza A viruses. This study also identifies influenza virus gene segments that appear to be incompatible for generation of reassortants. Elucidation of the molecular basis of this restriction may provide information on intergenic interactions involved in virion assembly or packaging.