Murphy B R, Sly D L, Tierney E L, Hosier N T, Massicot J G, London W T, Chanock R M, Webster R G, Hinshaw V S
Science. 1982 Dec 24;218(4579):1330-2. doi: 10.1126/science.6183749.
An influenza A reassortant virus that contained the hemagglutinin and neuraminidase genes of a virulent human virus, A/Udorn/72 (H3N2), and the six other influenza A virus genome segments from an avirulent avian virus, A/Mallard/New York/6750/78 (H2N2), was evaluated for its level of replication is squirrel monkeys and hamsters. In monkeys, the reassortant virus was as attenuated and as restricted in its level of replication in the upper and lower respiratory tract as its avian influenza virus parent. Nonetheless, infection with the reassortant induced significant resistant to challenge with virulent human influenza virus. In hamsters, the reassortant virus replicated to a level intermediate between that of its parents. These findings suggest that the nonsurface antigen genes of the avian parental virus are the primary determinants of restriction of replication of the reassortant virus in monkeys. Attenuation of the reassortant virus for primates is achieved by inefficient functioning of the avian influenza genes in primate cells, while antigenic specificity of the human influenza virus is provided by the neuraminidase and hemagglutinin genes derived from the human virus. This approach could lead to the development of a live influenza A virus vaccine that is attenuated for man if the avian influenza genes are similarly restricted in human cells.
一种甲型流感重配病毒，其含有强毒株人源病毒A/Udorn/72（H3N2）的血凝素和神经氨酸酶基因，以及无毒力禽源病毒A/野鸭/纽约/6750/78（H2N2）的其他六个甲型流感病毒基因组片段，在松鼠猴和仓鼠体内对其复制水平进行了评估。在猴子中，重配病毒与其禽流感病毒亲本一样减毒，且在上、下呼吸道的复制水平受到限制。尽管如此，重配病毒感染诱导了对强毒株人源流感病毒攻击的显著抗性。在仓鼠中，重配病毒的复制水平介于其亲本之间。这些发现表明，禽源亲本病毒的非表面抗原基因是重配病毒在猴子体内复制受限的主要决定因素。重配病毒对灵长类动物的减毒是通过禽流感基因在灵长类细胞中功能低效实现的，而人源流感病毒的抗原特异性则由源自人源病毒的神经氨酸酶和血凝素基因提供。如果禽流感基因在人细胞中同样受到限制，这种方法可能会导致开发出一种对人类减毒的甲型流感活病毒疫苗。
