达菲首次证实失效 流感变异的真相与忧虑？

　　

生物通报道，据Science Insider消息，丹麦国内一名猪流感（新流感H1N1）患者在治疗过程中对达菲产生耐药性，在达菲治疗失效后改用葛兰素史克公司的“乐感清”治疗。

 

目前该患者已经治愈出院，所幸这名丹麦患者自患病后一直在接受治疗，并没有将产生耐药性的毒株传播给其他人。

 

据悉，罗氏制药公司已证实达菲失效，这是科学家首次检测到甲型H1N1（新流感）对达菲产生抗药性。目前，罗氏公司正着手研究应对措施。

 

达菲为何失效？

要知道达菲为何失效，首先要了解达菲的工作机制。

 

达菲：是一种属于神经氨酸酶抑制剂家族的抗病毒物质。其目标是这些病毒表面上的一种酶，这种酶被称为神经氨酸酶蛋白质。当神经氨酸酶受到抑制时，病毒就无法走出庇护它们的细胞，并随后死掉，再也无法扩散和传染人体的其它细胞。神经氨酸酶是H1N1中的N（neuraminidase）所指代的一种酶。

 

新流感“N”变异

有专家推测，这次新流感首次表现出对达菲失效的原因在于病毒的神经氨酸酶突变。

 

早几年前，季节性流感病毒对达菲表现出耐药性就源自神经氨酸酶之故。2008年1月，科学家首次发现季节性流感病毒的神经氨酸酶H274发生突变，突变后的毒株对达菲具有抵抗力，但其传播能力变低。

 

这次丹麦新流感的耐药性专家推测可能也是H274Y作祟。不过类似的突变没有在其他患者身上出现，这表明这种突变是在病人接受治疗过程中的无害突变。

 

正因为此，科学家们对这一突变事件没有给予过多的关注。所幸，丹麦患者在治疗过程中出现变异，病毒并没有传播给其他人。

 

真正担忧的情况

专家表示，如果新流感耐药变异的同时还衍生出强大的传播能力那才令人担忧。因为，目前全世界甚至世界卫生组织都储备有大量达菲。毕竟，目前唯一能抵抗新流感的药物也只有罗氏的达菲和葛兰素的乐感清两种。一旦，达菲失效，可用药就只剩一种了。

 

不少专家表示，一旦新型流感毒株与季节性流感毒株杂交变异，那么对人类的威胁就升级了。

 

新流感在巴西与日本已证实变异

据媒体消息，日本一研究小组１８日发布的最新研究报告称，部分甲型Ｈ１Ｎ１流感病毒已出现变异。
 报告说，东京大学医学研究所教授河冈义裕领导的研究小组发现，变异发生在甲型Ｈ１Ｎ１流感病毒表面的血细胞凝集素上，这种刺状的流感表面蛋白承担着让病毒附着到人体细胞上的作用。研究人员通过分析一批甲型Ｈ１Ｎ１流感病毒，确认部分病毒的血细胞凝集素发生了变异。同样的变异之前在感染人类的Ｈ５Ｎ１型高致病性禽流感病毒中也发现过。

 

另据此间媒体报道，巴西圣保罗州卫生部门１６日宣布，巴西阿道弗·卢茨细菌学研究所的基因测序研究显示，与美国加利福尼亚州最初报告的甲型Ｈ１Ｎ１流感病例的样本相比，圣保罗州一名患者感染的甲型Ｈ１Ｎ１流感病毒的血细胞凝集素也发生了变化，这表明在一些地区病毒已经发生变异

（生物通 小茜）

 

生物通推荐原文阅读：

Tamiflu Resistance in Swine Flu No Cause for Concern—Yet

A Danish swine flu patient has developed resistance against the most widely used influenza drug, oseltamivir. But public health experts say there is no reason to be alarmed, because resistance developed while the patient was being treated—which suggests the resistant virus isn’t circulating yet—and she appears not to have infected other people. In a “threat assessment”  issued today, the European Centre for Disease Control and Prevention (ECDC) says that the finding “does not represent a public health threat.”

 

The specter of a pandemic strain that’s resistant to oseltamivir—also known as Tamiflu—worries flu experts because it could render countries’ massive stockpiles of the drug useless. They have seen this happen before: In the seasonal H1N1 strain, resistance has become rampant the past few years, thanks to a mutation in the virus’s neuraminidase gene called H274Y.

 

The emergence of that strain is a complex story. For many years, researchers occasionally saw H274Y appear in seasonal flu patients while they were being treated, but those viruses tended to not be very good at spreading to other people, so resistance never really caught on. But about 2 years ago, a seasonal strain appeared whose fitness is not diminished by the mutation—perhaps because other mutations compensate for it--—which explains why that strain has spread so fast, even in countries that use little oseltamivir.

 

H274Y is also responsible in the case of the Danish swine flu patient. But the fact that other patients in the Danish cluster did not have the mutation suggests that her resistance is the more innocuous kind that develops over the course of a patient’s treatment—which explains why scientists aren’t spooked yet.

 

If, like the seasonal H1N1, resistant pandemic virus finds a way to spread efficiently, however, the situation would be very different. Recently, some countries have added zanamivir (Relenza) and other drugs to their arsenal, but for many, oseltamivir is still the only weapon.