据6月4日的《科学》杂志报道说，具有密切关系效应的数种基因突变可能与抗药季节性流感病毒在全世界范围内的扩散机制有关。他们的发现也许可以帮助研究人员确认需要对哪一世系的病毒进行密切关注，看其是否有发生未来抗药性的迹象。 当抗药病毒在1998年首次被发现的时候，它还相对比较弱，并且在培养基和动物模型中的生长状态不佳。
到2008的时候，该病毒的活力增强并在世界各地传播，有效地排除了锋线药物达菲（Tamiflu）在季节性流感中的进一步使用。 抗病毒药物的广泛使用可导致耐药性的扩散，但达菲还没有被广泛用于治疗季节性的H1N1流感病毒。 那么，这一抗药性为什么会扩散的如此之快呢？ 该病毒遗传码的某一突变使得对达菲有抵抗力的季节性H1N1病毒能够与一种叫做神经氨酸苷酶的酵素结合。该酵素位于被感染细胞的表面。 Jesse Bloom及其同僚发现，这种叫做H274Y的突变可降低到达细胞表面的神经氨酸酶的量。就像是这类突变所常常发生的情况一样，这一突变可降低该病毒的适切程度，但文章的作者发现，有2种预先存在的继发性突变似乎可以弥补病毒适切程度恶化的效应。
一篇附随的Perspective对这一研究以及为什么H274Y会开始扩散的这一未被解答的问题进行了讨论。
原文出处：
Article #12: "Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance," by J.D. Bloom; L.I. Gong; D. Baltimore at California Institute of Technology in Pasadena, CA.
Several mutations with intimately linked effects are likely behind the worldwide spread of drug-resistant seasonal influenza virus, researchers report in the June 4 issue of Science. Their findings may help researchers decide which viral lineages to keep a close eye on for signs of future drug resistance. When the resistant virus was first discovered in 1998, it was relatively feeble and grew poorly in culture and animal models. By 2008, this virus was invigorated and had spread around the world, effectively ruling out further use of the frontline drug Tamiflu, or oseltamivir for seasonal flu. The widespread use of antiviral drugs can lead to the spread of drug-resistance, but oseltamivir hadn't yet been widely used for seasonal H1N1. So, why did resistance spread so fast? One mutation in the virus' genetic code that has made the seasonal H1N1 resistant to oseltamivir binds to an enzyme called neuraminidase on the surface of infected cells. Jesse Bloom and colleagues found that this mutation, called H274Y, reduces the amount of neuraminidase that reaches the cell surface. As such mutations usually do, this one reduces the virus' fitness, but the authors discovered two pre-existing secondary mutations that seemed to compensate for the deleterious effect on the virus' fitness. An accompanying Perspective discusses this work and the unanswered question of why H274Y started to spread at all.
