Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines.
Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines.
复制标题
四种病毒基因独立地导致甲型/安娜堡/6/60 (H2N2) 冷适应重配病毒活疫苗的减毒。
DOI：
10.1128/jvi.62.2.488-495.1988
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发表时间：
1988
影响因子：
5.4
通讯作者：
Murphy,BR
中科院分区：
文献类型：
--
作者：
Snyder,MH;Betts,RF;DeBorde,D;Tierney,EL;Clements,ML;Herrington,D;Sears,SD;Dolin,R;Maassab,HF;Murphy,BR
先前的临床研究证明，通过来自流感A/安阿伯/6/60（H2 N2）冷适应（ca）供体病毒与流行性野生型流感A病毒的交配的基因重配而衍生的活流感A病毒疫苗具有可再现的安全性、感染性、免疫原性，并且在预防由用毒性野生型病毒攻击引起的疾病中是有效的。这些甲型流感病毒疫苗也在体外表达ca和温度敏感性（ts）表型，但尚未充分确定ca病毒亲本的基因，这些基因可指定ca、ts和减毒（att）表型。为了鉴定与这些表型相关的基因，我们分离了6个单基因替换抗性病毒，每个病毒仅从ca亲本病毒继承一个RNA片段，其余7个RNA片段来自A/Korea/1/82（H3 N2）野生型病毒亲本。在体外评估了它们的ca和ts表型，在雪貂、仓鼠和血清阴性的成年志愿者中评估了att表型。我们发现，聚合酶PA基因的CA父母指定的CA表型和PB 2和PB 1基因独立指定的TS表型。ca供体病毒的PA、M、PB 2和PB 1基因各自促成att表型。ca供体病毒的四个基因对att表型有贡献，这一发现为观察到的ca复制体病毒在人体内复制后的表型稳定性提供了部分解释。
Clinical studies previously demonstrated that live influenza A virus vaccines derived by genetic reassortment from the mating of influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus with epidemic wild-type influenza A viruses are reproducibly safe, infectious, immunogenic, and efficacious in the prevention of illness caused by challenge with virulent wild-type virus. These influenza A reassortant virus vaccines also express the ca and temperature sensitivity (ts) phenotypes in vitro, but the genes of the ca virus parent which specify the ca, ts, and attenuation (att) phenotypes have not adequately been defined. To identify the genes associated with each of these phenotypes, we isolated six single-gene substitution reassortant viruses, each of which inherited only one RNA segment from the ca parent virus and the remaining seven RNA segments from the A/Korea/1/82 (H3N2) wild-type virus parent. These were evaluated in vitro for their ca and ts phenotypes and in ferrets, hamsters, and seronegative adult volunteers for the att phenotype. We found that the polymerase PA gene of the ca parent specifies the ca phenotype and that the PB2 and PB1 genes independently specify the ts phenotype. The PA, M, PB2, and PB1 genes of the ca donor virus each contribute to the att phenotype. The finding that four genes of the ca donor virus contribute to the att phenotype provides a partial explanation for the observed phenotypic stability of ca reassortant viruses following replication in humans.