H1N1病毒的"来龙去脉"

臭棋 · 发表于 2009-5-16 07:28

How Time and Mutations Engineered the New H1N1 Strain

H1N1病毒的"来龙去脉"

By David Brown
Washington Post Staff Writer
Monday, May 11, 2009
华盛顿邮报特派记者大卫•布朗
2009年5月11日

Once Upon a Time there was a little flu virus. It was probably born in Kansas in late 1917 or 1918, although nobody is really sure. Its name was H1N1. It grew up to be very wicked.
1917年或1918年末（时间没人能够确定）在堪萨斯州曾出现过一种相当厉害的小型流感病毒，这种病毒就是H1N1.

The story of the new strain of swine influenza now circling the world actually starts a lot farther back than the 20th century, but the year the "Spanish influenza" appeared is a good place to start.

阴影笼罩着全世界的新型猪流感的故事可以追溯到20世纪以前很久很久，而当年的西班牙流感可以做为一个不错的开头。

From the second week in March 1918, when soldiers at an Army camp in Kansas began to get ill, until the final mini-waves of 1920, the Spanish flu infected about 97 percent of the people on Earth and killed at least 50 million of them.

自1918年3月的第二个周堪萨斯一个军营开始有病例出现，直到1920年最后的一波小流行，西班牙流感感染了地球上97%的人，并且导致了至少5千万人死亡。

The virus probably came from waterfowl, which carry dozens of different flu viruses. At some point, either before or after it got into human beings, the virus got into pigs, a species that can be infected by avian and human strains. It has stayed in swines ever since, and in people for almost as long.

这种病毒可能来自于携带数十种流感病毒的水禽。在这种病毒进入人体之前或之后，其进入了猪的体内（猪是一个可以同时感染禽型流感和人型流感的物种），此后它便一直停留在猪的群体内，在人群中可能也存在了同样长的时间。

The swine-origin influenza A (H1N1) virus circulating in Mexico, the United States and Canada, and present in two dozen other countries, is a descendant of the Spanish flu H1N1 virus. In the past 90 years, though, a lot of new blood -- metaphorically speaking -- has entered its lineage. It does not look or act much like its notorious ancestor.

猪流感的病原甲型H1N1流感病毒现在正在墨西哥美国加拿大流行，在其他二十几个国家也有病例出现。这种病毒就是当年西班牙流感H1N1病毒的后裔。在过去的90年里，许多“新鲜血液”注入到它的谱系中，所以它在外观上或表现上已经不太像其臭名昭著的祖先了。

This might be a good place to address this A and H and N business.
这样可能需要解释一下A,H,N的含义

Influenza virus is part of a family called Orthomyxoviridae. There are four sub-classifications -- influenza virus A, influenza virus B, influenza virus C and thogotoviruses. It's like citrus fruit, which encompass oranges, lemons, limes, grapefruit, etc.

流感病毒是正粘病毒科家族的一部分，有四个亚型——甲型流感病毒，乙型流感病毒，丙型流感病毒和thogotoviruses。（就像柑橘属水果包括柑桔，柠檬，酸橙，葡萄柚等）

Influenza A and B cause illness in people; the others almost never do. There are many, many types of influenza A but only one influenza B.

甲型和乙型流感病毒可以导致人类发病，而其他类型的流感病毒几乎不感染人。甲型流感病毒分许多型，而乙型流感病毒只有其自己一型。

The diversity of influenza A arises from variations in the two proteins on its surface, called hemagglutinin (abbreviated H or HA) and neuraminidase (N or NA). Together, the proteins make up the face that a flu virus presents to the immune system of a bird, a pig or a human being.

甲型流感病毒的多样性来源于其表面两种蛋白的变化，这两种蛋白就是血凝素（简称A或HA）和神经氨酸酶（简称N或NA）。这两种蛋白组成了流感病毒提呈到鸟，猪或人体免疫系统的表面抗原。

In this setting, the face's appearance is no small matter. The immune system's ability to recognize a virus is one of the first steps in stopping it.

因此，这种表面抗原形态表现的影响就非同小可了，因为免疫系统识别一种病毒是阻止其感染的第一步。

One strategy involves antibodies. They attack only if they are tailor-made for the virus, which requires the immune system to get a good look at the surface proteins. The immune system can offer the best protection if it has seen the pathogen before and has the right antibodies ready.

免疫防御的一种策略就是抗体，抗体是一种根据病毒表面蛋白而产生的特定的蛋白，只能攻击与其匹配的抗原，这一过程就需要免疫系统很好的识别病毒表面蛋白。如果曾遇到过某种病原并有相应的抗体存在，那么免疫系统能够提供最好的防御。

Think of H as hair and N as nose, two features for learning and remembering the identity of a virus. In the world of influenza A, there are 15 subtypes of H (straight blond, wavy red, short black, kinky black, etc.) and nine subtypes of N (Roman, ski jump, flared, long, etc.). Each subtype is numbered -- H1N1, H3N2, H9N2 and so forth.

把H比喻为头发,N比喻为鼻子，这便是识别和记忆一种病毒的特征。在甲型流感病毒家族里有15个H亚型(好比直金发，红卷发，黑短发，扭结黑发等)和9个N亚型（鹰钩鼻，上翘鼻，钟形鼻子，长鼻子等）。每个亚型都编号如——H1N1, H3N2, H9N2等。

H1N1 is simply one combination of two of these subtypes that give the virus an appearance recognizable to the immune system -- say, short black hair and a long nose. Within these subtypes, however, there are subtle -- and sometimes not so subtle -- variations. They arise from mutations in the genes governing the H and N proteins.

H1N1是这些亚型中两个的简单组合，也是其能被免疫系统识别的外观（好比黑短发和长鼻子）。然而在这些亚型中有时有（有时也没有）一些微细的变化，这些变化源自于编码H和N蛋白的基因的突变。

Over time, an H1N1 influenza A virus can change its appearance significantly through random mutation. It can streak its short black hair and put a gold stud in its long nose one year, and shave its hair into a Mohawk and add a diamond stud in the other nostril the next. Pile up enough of these, and pretty soon the immune system no longer recognizes it as the virus with the short black hair and the long nose it once knew -- even though it still fits that description.

随着时间的推移，甲型H1N1病毒通过自由突变可以使其外观发生显著地变化（好比某年在黑短发中加上花纹，在长鼻子上加上黄金钉子，下一年又把头发理成Mohawk型并且在一个鼻镶上一颗钻石）。这些变化积累的足够多时，很快免疫系统就不能识别这种病毒了，尽管其仍然完全符合原来的性状。

That is why the Spanish flu virus, the new swine flu virus and some of the human flu viruses circulating in recent winters can all be H1N1 viruses and yet look and behave so differently.

这就是西班牙病毒，新型猪流感病毒和近期在冬季流行的人流感病毒能够有如此不同的表现的原因。

Research in the past few years on the Spanish flu virus -- which has been reconstructed from fragments extracted from lung-tissue samples from people who died in 1918 -- has revealed that much but not all of its killing potential resided in the H protein. One of the reassuring things about the new swine flu strain is that it does not have those same "virulence factors," even though it shares the same broad H1N1 features.

过去几年对西班牙流感病毒的研究（把从死于1918年流感患者肺组织样本上提取的片段进行改造）揭示其大多数杀伤能力位于H蛋白。新型猪流感令人安慰的一点是其不具有那些毒性因子，尽管其广泛具有H1N1病毒的特性。

Studies done in the past two weeks suggest that people who have received flu shots in the past few years -- shots that protect against the most common human H1N1 strain in circulation -- are not protected against this swine flu strain, even though it also is H1N1. Why? Because it looks so different to the immune system that the virus-killing antibodies do not react.

过去两周的研究表明几年前接种流感疫苗（预防大多数流行中普通人H1N1流感株的疫苗）不能预防这种猪流感病毒，尽管其也是H1N1。为什么呢？因为对免疫系统来说这种病毒很陌生，病毒杀伤抗体不能起作用。

Such is the importance of looks, immunologically speaking.
这就是免疫学角度上说的外表的重要性

The human H1N1 flu virus -- and it's "human" only because it is in us -- that circulates each winter changes a little bit year to year in a phenomenon called "antigenic drift" as mutations creep into the H and N genes. But it can also change much more rapidly through something called "antigenic shift," which happens when entire H or N proteins (or both) are swapped out wholesale for new versions.

每个冬季都流行的人H1N1流感病毒（称其为人型只是因为其在我们人类流行）每年都变化一点，这种现象叫做抗原漂移，突变发生于H和N基因。然而它能以抗原漂变来更快的变化，抗原漂变是指整个H或N蛋白被新的类型完全替代。

This is possible because influenza's genes are on eight separate strands, or "gene segments." One or two or more can be replaced, like cards in draw poker.

这是有可能的，因为流感病毒的基因在8个独立的链上或者基因片段上。一个或两个或更多的基因可以被替代，就像draw poker中的卡片一样。

That's a rare event, however, and requires that two flu strains invade a single cell, replicate and then get their products mixed up in the packaging. The result is a virus dramatically different in immunological appearance, and sometimes in disease-causing capability, from either parent.

然而这是罕见的，而且需要两种流感病毒进入同一个细胞中，复制然后在包装过程中其产物混合。这样的结果是一种病毒在免疫外观上变得显著不同，有时能从其一个母代中获得致病能力。

One way or another, a new influenza virus with the identity of H2N2 appeared in 1957. Because it was a new combination, nobody had immunity. It was called "Asian flu," and it spread everywhere, outcompeting H1N1 strains, which disappeared in people but remained in pigs.

无论如何，1957年一种新的流感病毒出现了（确定为H2N2型）。因为其实一个结合体，没有人有免疫力。它就是“亚洲流感”，它四处流行，胜过了H1N1型流感，然后在人群中消失了但是仍然村留在猪体内。

In 1968, another strain, an H3N2 combination, appeared on the scene. Nobody had immunity to it either. It had a world's worth of susceptible victims and caused the "Hong Kong flu" pandemic that year and the next.

1968年，另一株流感病毒以H3N2组合出场。同样，人们对其没有免疫力。对该病毒全世界性的易感，导致了当年及次年“香港流感”的大流行。

In 1977, a strange thing happened. The H1N1 virus, absent for years in people, reappeared. Curiously, it was almost exactly like the last strains in the 1950s. It was so close, in fact, that many people suspect it was released into the world by mistake from 1950s samples kept in a lab freezer.

1977年，奇怪的事情发生了，在人群中消失多年的H1N1病毒重新出现了，奇怪的是，它几乎就像1950年的最后那株一样，因为太相似所以有很多人怀疑这是由于失误导致实验室冰箱中1950年的样品泄露出来所致的。

Whatever the source, it spread widely as the "Russian flu," infecting lots of people born after the disappearance of H1N1 two decades earlier.
无论来源怎么样，它产生了广泛的流行也就是“俄罗斯流感”，感染了许多在H1N1 20年前消失后出生的人。

Since then, H1N1 and H3N2 strains have been circulating, mutating in small ways, and infecting new victims year to year. At the moment, the dominant H1N1 strain is one called A/Brisbane/59/2007. By chance, the dominant H3N2 strain was also found in Brisbane, Australia, in 2007 and is named A/Brisbane/10/2007. Influenza B, which has caused about one-third of infections in the United States this flu season, is dominated by a strain called B/Florida/04/2006.

从那以后，H1N1和H3N2病毒株一直流行，并有一些小的突变，每年都有新的受害者被感染。那时主导地位的H1N1株式被称为A/Brisbane/59/2007，偶然的是主导地位的H3N2株也在2007年于澳大利亚Brisbane市发现，于是命名为A/Brisbane/10/2007。占美国这个流感季节的感染流感人数约三分之一人的乙型流感是由B/Florida/04/2006株引起的

But now comes a whole new H1N1 virus. It is formally labeled A/California/04/2009 (see graphic), and it was taken from a 10-year-old boy in San Diego who came down with the flu on March 30. It has an H from an H1N2 virus circulating in American pigs and an N from an H1N1 virus found mostly in Eurasian ones.

但是现在迎来了一个全新的H1N1病毒，它被正式标记为A/California/04/2009（见图片），这是3月10号从患这种流感的一个10岁的San Diego男孩体内取得的，它的H来自正在美国的猪中流行的H1N2病毒，N来自于主要感染欧亚混血儿的H1N1株。

Our immune systems, familiar with other H's and N's, do not know what to make of it. We have no antibodies against the combination, so we have no protection against it. And we will generate antibodies only if we get infected by the virus or vaccinated with a killed version of it; either way will teach the immune system what it looks like.

我们的免疫系统熟悉其他H和N, 但不知道如何处理这种病毒。我们没有抗体对付这种结合体，所以我们对其没有防御能力。只有我们感染了这种病毒或接种了灭活的疫苗才能产生相应抗体，因为这两种方法均可以让我们的免疫系统认识这种病毒。

This is the swine flu or, as the federal government likes to call it, confusingly but inoffensively, the H1N1 strain.
这就是猪流感，或者就像联邦政府愿意称呼的那样，H1N1株，尽管有些令人迷惑但是没有害处。

It's coming soon to a neighborhood near you. But we don't yet know how this tale will end.
说不定它很快就会出现在你身边的人身上，但我们还不知道如何才能阻止它流行。

臭棋 · 发表于 2009-5-16 07:38

H1N1病毒的"来龙去脉"

华盛顿邮报特派记者大卫•布朗
2009年5月11日

很久以前,有一种名叫H1N1的小病毒出现了.这很可能是发生在1917年或1918年年末的堪萨斯州,但是不能肯定.这种病毒成了一种非常罪恶的病毒.
如今,新型猪流感病毒在全球徘徊.关于它的故事可追溯到20世纪之前很久.然而,西班牙流感的发生是一个合适的起点.
自1918年三月的第二周在堪萨斯州军营的士兵开始生病到1920年最后的余波,西班牙流感感染了全球约97%的人,造成其中至少5千万人死亡.这种病毒可能来源于水禽.水禽携带几十种不同的流感病毒.一种既可以感染禽类又可以感染人类的病毒,在入侵人类之前或之后的某一时刻感染了猪.从那以后,该病毒留传于猪体内.它居留在人类的历史几乎一样久远.猪流感A(H1N1)病毒正在墨西哥,美国和加拿大肆虐.其他20多个国家也有病例发生.该病毒是西班牙流感H1N1病毒的一个子代.不过,90年过去了,它的血统又注入许多新鲜的血液.如今流行的猪流感病毒看来与它臭名昭著的前辈不太一样.
这或许是一个好的场合来讲解A、H和N的意义。流感病毒属于正黏液病毒科，包括四类：流感病毒A、流感病毒B、流感病毒C和托高土病毒。这就类似于柑橘类水果包括橘子、柠檬、酸橙、葡萄柚等一样。流感病毒A和流感病毒B使人类致病，其它类病毒几乎不致病。流感病毒A可分许多亚型，而流感病毒B不分。流感病毒A的多样性缘于其表面的两种蛋白，这两种蛋白分别称为血球凝集素（简写成H或HA）和神经胺酸酶（简写成N或NA）。这些成分一起构成了禽流感病毒呈递给鸟、猪和人的免疫系统的表面蛋白，在这种情况下，禽流感病毒表面的外形不可小觑。免疫系统能识别病毒是阻止其入侵的前提。有一种抵抗病毒的方法涉及到抗体。特定的抗体才能对相应的病毒发出攻击，因此，这就需要免疫系统能精确识别病毒的表面蛋白。如果免疫系统以前曾接触这种病原体，并且已经产生了特定的抗体，那么，免疫系统才能提供最佳保护。
想象一下，H和N分别是病毒的头发和鼻子，这是识别和记忆一种病毒的两个特征。对于流感病毒A，H分为15个亚型（直的金发、红波浪卷、黑短发、黑卷缩发，等），而N分为9个亚型（鹰鼻、细腰鼻、长鼻，等）。每个亚型给以编号—H1N1、H3N2、H9N2等等。H1N1仅仅就是两种亚型蛋白的组合（类似于黑短发和长鼻子），这样免疫系统才能识别。然而，在这些亚型中会有微妙的变异，甚至有时变异较大。这是因为表达H和N蛋白的基因发生了突变。
随着时间的推移，A型禽流感病毒通过随机突变会明显改变它的外表。某一年，它可以将黑短发加上条纹，在长鼻子上镶嵌金纽扣，再后一年，它修剪莫霍克发型，用钻石纽扣装饰另一鼻孔。这些改变累积多了，免疫系统很快就不再将其看作当初认识的黑短发、长鼻子的那个病毒了。尽管该病毒还符合那个描述。为什么西班牙流感病毒，新猪流感病毒以及近几年冬天流行一些的人流感病毒都叫H1N1病毒，但它们的外表举止却如此不同呢？这就是原因。自1918年死亡患者的肺组织样品提取的病毒片段已被重组成西班牙流感病毒。在过去的数年里，有关西班牙流感病毒的研究表明其致病性主要（并非全部）在于H蛋白。尽管新型猪流感病毒拥有广义的H1N1病毒的特征，但是，值得安慰的是该病毒没有相同的致病因子。
近两周研究表明，近几年感染过流感的人对新猪流感病毒并无抵抗力，虽然他们对大多数普通H1N1流感有抵抗作用。原因何在？因为新猪流感病毒对于人体免疫系统来说是如此与众不同，杀伤病毒的抗体不发挥作用。
这就是免疫学上讲的外表的重要性了。人H1N1流感病毒（所谓“人”是因为它发生于我们人类）每年冬天流行，逐年改变一点点，这种现象称作“抗原漂移”，其原因是H基因和N基因渐渐发生突变。通过“抗原转换” 人H1N1流感病毒也可以发生急剧变化，这时整个H或（和）N蛋白被新版替换了。因为流感病毒基因位于八个独立段（也称作基因片段），一个或两个或更多的基因被替换，就象暗扑克游戏中的纸牌一样。有这样一种罕见的情况。两株流感病毒入侵同一个细胞，复制，在组装过程中它们的产物混合，结果导致病毒免疫表型发生巨大的变化，有时致病性发生改变。不管以哪种方式，1957年一种新流感病毒以H2N2的身份出现了。因为它是一种新的整合体，当时无人具备免疫力。这被称为“亚洲流感”，四处传播，远胜于H1N1株病毒。它在人类消失了，但仍然存在于猪体内。
1968年，另一株流感病毒以H3N2组合出场。同样，人们对其没有免疫力。对该病毒全世界性的易感，导致了当年及次年“香港流感”的大流行。
1977年，一件奇怪的事情发生了。在人类销声匿迹数年的H1N1病毒重出江湖了。蹊跷的是，它与20世纪50年代最近的一株H1N1病毒几乎一模一样。因为是如此地相似，事实上许多人怀疑因为失误H1N1病毒从保存20世纪50年代那批标本的实验室冰柜中释放了。不管它来自何方，很快蔓延，感染了很多20世纪50年代H1N1病毒消失后出生人们。这次流行被称为“俄罗斯流感”。
从那以后，H1N2和H3N2病毒一直流传，细微突变，年复一年感染新的易感人群。那时，主要的H1N1病毒株被称为A/Brisbane/59/2007。意外地，2007年主要的H3N2病毒株也是发现在澳大利亚的布里斯班，被命名为A/Brisbane/10/2007。大约导致美国流感季节1/3的感染发生的流感病毒B被命名为B/Florida/04/2006。不过，现在一个全新的H1N1病毒出现了。它被常规命名为A/California/04/2009，它来源于一个圣地牙哥的10岁男孩。这个男孩在3月30日生病了。这个全新的H1N1病毒的H蛋白来源于在美洲猪之间流行的H1N2病毒，而其N蛋白来自于主要发生在欧亚人中的H1N1病毒。我们的免疫系统对于其它的H蛋白和N蛋白熟悉，但是不知如何对付这种新病毒。我们没有抗这种组合的抗体，所以我们对它毫无防备。只有我们感染了这种病毒或者接种了这种灭活病毒的疫苗，我们才能产生抗体。无论哪种方式均会告知机体免疫系统这种病毒的模样。
这就是猪流感，或者如联邦政府乐于称作的H1N1 病毒株，这个名称另人迷惑却也无可否认。它正靠近你。我们不知道这个故事如何结束。

臭棋 · 发表于 2009-11-23 00:34

:sm42:

H1N1病毒的"来龙去脉"

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逛了这许久，何不进去瞧瞧