The root of the pandemic influenza A(H1N1) virus could stem from the movement of pigs between Eurasia and North America or from the human production of multivalent vaccines. Those are two theories explored by Australian researchers in a study published online Nov. 24 in Virology Journal.

The search for the cause of pandemic H1N1 influenza “must be intensified while the clues are still fresh,” wrote the researchers, who were led by Dr. Adrian J. Gibbs, a virologist and an emeritus faculty member at Australian National University in Canberra. “The possibility that human activity may have had some role in its origins should not be dismissed without a dispassionate analysis of all available evidence. If we wish to avoid future pandemics, rather than just minimizing the damage they cause, we must better understand what conditions produce them.”

One possibility is that H1N1 emerged from unsampled pig herds in certain parts of the world, allowing the “ancestors” of the human H1N1 virus to have gone unnoticed for several years, according to Dr. Gibbs and his associates. This theory “depends on the intercontinental movement of live infected pigs, and requires at least two quarantine breaching incursions involving three different countries,” the researchers noted (Virology Journal 2006; 6:207 doi:10.1186/1743-422X-6-207). “It is likely that quarantine control of the spread of swine influenzas around the world varies greatly in its efficacy. However, viruses of the Eurasian ‘avian-like’ lineage, and their genes, have never been found in North America before [H1N1] appeared, even though they have been common in Europe for over three decades, and similarly ‘triple reassortant’ viruses and their genes have not been isolated in Europe, although they have been the dominant swine influenza virus in North America for more than a decade.”

In an interview, Tom Skinner, a spokesperson for the U.S. Centers for Disease Control and Prevention, Atlanta, described the possibility that H1N1 is product of three strains from three continents as “very unlikely. Each of the gene segments from this particular virus have been found in pigs for more than 10 years prior to the beginning of this outbreak.”

In addition, he said, a 2009 published study demonstrated that reassortant influenza viruses with genes from North American and Eurasian pigs were found in samples collected from pigs in Hong Kong as early as 2004 (Nature 2009;459:1122-5).

A second possibility proposed by Dr. Gibbs and his associates is that H1N1 emerged from vaccine production, either as a reassortant produced during research or during production of multivalent vaccines. “Multivalent ‘killed’ vaccines are mixtures of virions that have been grown in hen’s eggs and then chemically sterilized,” the researchers wrote. “Thus a reassortant might be produced if insufficient sterilant, usually formaldehyde or propiolactone, is added to the virion mixture. The live mixture could then infect pigs ‘vaccinated’ with it, and the growing viruses could reassort, infect piggery staff and hence spread to the broader human population.”

Mr. Skinner of the CDC said it is improbable that H1N1 emerged from laboratory work. “The evidence suggests that this is a virus that has evolved over time,” he said. “This particular virus doesn’t seem to have any kind of adaptations that would be typical of viruses that are grown or created in a laboratory. For example, if you use standard methods to grow influenza viruses in laboratories and you inject influenza virus into fertilized egg, the 2009 H1N1 influenza virus lacks properties that are associated with growth in egg. Based on everything we’ve seen it appears to be a naturally-evolved virus.”

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

大流行性甲型(H1N1)流感病毒的产生可能源于猪在欧亚大陆和北美洲之间的运输，抑或源于人类的多价疫苗生产活动。在11月24日《病毒学期刊》(Virology Journal)在线发表的一项研究中，澳大利亚研究者对上述两种理论进行了探讨。

 

该研究牵头人Adrian J. Gibbs博士是位于堪培拉的澳大利亚国立大学的病毒学家和荣誉退休教授。他与同事在文中写道，“必须趁线索尚新的时候，加大”关于大流行性H1N1流感原因的研究的力度。“在没有对所有现有证据进行客观分析的情况下，不应排除该病毒起源于人类活动的可能性。如果我们希望在未来避免流感大流行而不仅仅是将其造成的损害减至最低，那么我们必须更好地了解病毒产生的条件。”

 

Gibbs博士及其同事认为，一种可能性是，H1N1病毒可能源于世界某个地方未被采样检查的猪群，这使得人H1N1病毒的“祖先”多年来一直未被注意。研究者指出，该理论“的依据是活感染猪的洲际间运输，而这需要涉及到3个不同国家至少2次违反检疫规定将感染猪放行入关”(Virology Journal 2006; 6:207 doi:10.1186/1743-422X-6-207)。 “世界各国检疫控制猪流感传播的力度可能存在较大差别。 然而，在H1N1出现之前，欧亚大陆的‘禽样’病毒系及其基因在北美从未被发现，即使它们已在欧洲存在了30年以上，同样地，‘三源基因重配’病毒及其基因在欧洲也从未被发现，尽管它们作为主要猪流感病毒已在北美存在了10年以上。”

 

亚特兰大美国疾病控制预防中心(CDC)的发言人Tom Skinner在接受采访时表示，H1N1病毒来自3大洲3种病毒株的重配株的可能性“微乎其微”。 在此次流感暴发的10多年前，研究者就已在猪中发现该特殊病毒的各个基因片段。

 

此外，他表示，一项发表于2009年的研究显示，早在2004年，研究者就已在采集自香港猪的样本中发现了携带北美和欧亚猪的基因的重配流感病毒(Nature 2009;459:1122-5)。

 

Gibbs博士及其同事提出的第二种可能性是，H1N1病毒可能源于疫苗生产活动，包括生产重配病毒的研究期间或多价疫苗的生产期间。研究者写道，“多价‘灭活’疫苗是生长于鸡蛋中、随后经过化学灭菌的病毒粒子的混合物。” “因此，如果将灭菌不完全的(通常是)甲醛或丙内酯加入该病毒粒子混合物中，则可能产生重配病毒。‘接种’这种活混合物的猪可因此感染，并且这些生长的病毒可重配、感染猪场的猪，并由此传播至更广泛的人群。”

 

CDC发言人Skinner先生称，H1N1病毒不可能来源于实验室工作。他说，“有证据表明，这是一种随时间进化的病毒。这种特殊病毒没有实验室培养或制造的病毒所特有的任何适应能力。例如，如果采用标准方法在实验室中培养流感病毒，则需要将流感病毒注入受精卵中进行培养，而2009年H1N1流感病毒并没有表现出与卵培养相关的特性。基于我们所观察到的证据，它是一种自然进化的病毒。”

 

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