Science：1918致命流感真相

　　

生物通报道，1918大流感，有科学家认为病毒来自禽流感，这个差不多被认定为常识的定论，被科学家用新的证据推翻了，Science网站头条报道了这一文章，Don’t Blame Birds for 1918 Flu。

 

80年前，1918流感带走了全世界2000万人， 灾难早已远去，然而，科学家们对这场灾难的理解，对病毒起源的争议仍旧没有停下。

 

2005年，华盛顿军方病理学研究所的病毒学家Jeffrey Taubenberger和同事报道了1918流感病毒的全基因组序列，包括了之前未报导（Nature  437, 889–892; 2005）的最后三基因（编码聚合酶）序列。

 

病毒来自鸟类

该病毒的八个基因全长序列支持了之前观点：病毒完全来源于鸟类，而不是人类、鸟类来源的病毒序列的重配（reassortment）。检查聚合酶蛋白中有差异的十段序列，研究者发现1918和之后的人流感病毒的序列与鸟类病毒的有所不同，暗示这些区域对于病毒感染人是非常重要的。Terrence Tumpey和同事们使用了这个最末的基因组序列来重塑1918流感病毒，并研究了它在小鼠身上的毒力情况（Science  310, 77–80; 2005）。结果发现，这个病毒株的毒力非常强，可以在3到5天内杀死小鼠，而且病毒水平比其他感染性病毒株高出50倍。Tumpey同时还发现：1918红血球凝集素（hemagglutinin）和聚合酶基因也是促使该病毒株毒力明显高出其他流感病毒株的重要原因。之前也有学者支持这一论断。

 

被冤枉的鸟类

多年来，1918大流感病毒起源自鸟类的论断几乎成为常识。然而，一项新的研究推翻了这一论点。

 

研究者认为，1918流感毒株在传染到人身上时已经在哺乳动物体内循环，如猪和人，这个过程在1918年以前的好几年内。经过多次的基因片段的交换后，才慢慢转变为杀人的1918流感病毒。

 

St. Jude Children's Research Hospital 的Robert Webster等人将1918-1930年间的数千条基因序列进行分析，并用分析软件会展病毒进化树。

 

这些分析数据表明，1918流感病毒可能在1918年前已经在猪或是人群中传播了至少2年或15年左右，直到后来发生基因交换变异为致命性病毒。香港大学的Gavin Smith表示，这些数据表明，1918流感病毒实在不宜说起源自鸟类。Gavin Smith是负责这次研究的数据计算机分析人员。

 

牛津大学的进化生物学家Olive Pybus表示，我认为这是个可信的结果。美国NIH旗下过敏与传染病研究所的Taubenberger则不认同这一结论。

（生物通  小茜）

 

生物通推荐原文阅读：

Don’t Blame Birds for 1918 Flu

It has become almost common wisdom that the virus that caused the 1918 flu pandemic was an avian strain introduced into the human population shortly before the pandemic erupted. But a new study disputes that hypothesis, arguing instead that genes of the 1918 virus had circulated in mammalian hosts, most likely pigs and humans, for several years before 1918. Multiple gene-swapping events brought them together in a single killer strain, say the researchers; improving surveillance in humans and in swine could alert scientists to such events early in the future.

The origins of the 1918 virus, which is estimated to have killed at least 20 million people, are still controversial. After painstakingly piecing together the genome of the extinct strain, a team led by virologist Jeffery Taubenberger, then at the Armed Forces Institute of Pathology in Washington, D.C., concluded in 2005 that the virus most closely resembled viruses of avian origin; the team suggested it had become transmissible between humans after a couple of key changes (Science, 7 October 2005, p. 28). The study made many headlines, in part because of the fear that the H5N1 avian influenza virus, which so far transmits poorly between humans, could undergo a similarly fateful transformation. But others have questioned Taubenbergers's conclusions.

 

To study the origins of the three 20th century pandemic flu viruses, Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee, and his colleagues took DNA sequences of thousands of flu isolates dating back as far as the 1930s--as well as the 1918 strain--and fed them into models that calculate the most likely evolutionary relationships between them. They report today in the Proceedings of the National Academy of Sciences that genes of the 1918 virus were most likely present in swine or human hosts at least 2 and possibly 15 years before the pandemic began and combined to form the deadly virus during multiple reassortments, presumably rare events in which flu viruses exchange genes. "The data don't really fit with the idea that it was a recent avian introduction," says Gavin Smith of the University of Hong Kong, who carried out the computational analysis.

 

"I think it's a reasonable conclusion," says Oliver Pybus, an evolutionary biologist at the University of Oxford in the United Kingdom, "although personally, I'd still leave the door open" for an avian origin. Taubenberger, now at the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, is not convinced. He points out that relying on sequences from the 1930s and '40s, the early days of influenza science, is tricky, because the viruses ratcheted up mutations as they were grown in animals. He also points out that although veterinarians have recognized flu in horses for centuries, flu in pigs wasn't described until 1918, which seems odd if the virus was present several years earlier. The bottom line, however, is that data are so scant that scientists can never fully know what happened before 1918, Taubenberger says.

 

The study has a practical upshot, the authors say. In flu surveillance, researchers look primarily for the genes encoding the virus's surface proteins, hemagglutinin and neuraminidase; if they sequence the so-called internal genes as well, they might detect new genes slipping into human virus strains in the run-up to a pandemic, they say. In addition, surveillance in pigs should be expanded, says Webster--although he doubts that anyone will make the money available to do so.