Novel strategies and basic approaches for the study of the treatment against highly pathogenic influenza virus.

甲型流感病毒可以感染各种不同的宿主，因此必须适应不同的宿主温度才能有效地进行病毒复制。众所周知，PB2亚基与温度敏感性有关。另一方面，PA亚基在热敏性中的作用仍然知之甚少。为了测试哪些聚合酶亚基参与了热应激，我们在核糖核蛋白（RNP）复合体中重组了流感RNA聚合酶的人工杂交株，并测量了mRNA、cRNA和vRNA在不同温度下的稳态水平。PA亚基参与了热胁迫下RNP活性的调节。PA亚基的残基114是该活性的重要决定因素。这些发现提示甲型流感病毒可能通过RNA聚合酶基因的重组获得适应宿主不同体温的RNA聚合酶。因此，我们为研究抗流感病毒的新药和治疗方法提供了新的途径。

Influenza A virus can infect a variety of different hosts and therefore has to adapt to different host temperatures for its efficient viral replication. It is well known that the PB2 subunit is involved in temperature sensitivity. On the other hand the role of the PA subunit in thermal sensitivity is still poorly understood. To test which polymerase subunit(s) were involved in thermal stress we reconstituted artificial hybrids of influenza RNA polymerase in ribonucleoprotein(RNP) complexes and measured steady-state levels of mRNA, cRNA and vRNA at different temperatures. The PA subunit was involved in modulating RNP activity under thermal stress. Residue 114 of the PA subunit was an important determinant of this activity. These findings suggested that influenza A virus may acquire an RNA polymerase adapted to different body temperatures of the host by reassortment of the RNA polymerase genes. Thus, we have introduced the new way to study novel drugs and treatments against influenza virus.