The deadly H1N1 influenza virus that’s fueling fears of a global pandemic is a hybrid of two common pig flu strains, scientists who have studied the disease told Wired.com Tuesday. Earlier reports called it a combination of pig, human and avian influenza strains.
The findings may resolve some uncertainty about the nature of the virus, but much is still unknown about its origins and effects.
“This is what we call a reassortment between two currently circulating pig flu viruses,” said Andrew Rambaut, a University of Edinborough viral geneticist. “Why it’s emerged in humans is anyone’s guess. It hasn’t been seen before in pigs as far as I know.”
Rambaut analyzed the gene sequences of viral samples taken from two infected California children. The samples were collected by the Centers for Disease Control and Prevention, and made available to researchers through an international database of flu genomes.
His conclusions were echoed by Eddie Holmes, a virus evolution specialist at the University of Pennsylvania, and Steven Salzberg, a University of Maryland bioinformaticist. Both have looked at the CDC-provided sequences. The CDC could not be reached for comment, but a document released to scientists and obtained by Wired.com affirms their analysis.
Researchers believe the samples from California represent the same viral strain as one that is believed to have killed as many as 150 of an estimated 1,600 hospitalized Mexicans, and caused hundreds more infections worldwide, including at least 64 in the United States. However, as samples from Mexico have not yet been sequenced, the similarity is not conclusive.
The two strains whose genes are found in the California samples belong to influenza families known generally as North American and Eurasian pig flu. The former was first described in the 1930s, and the latter in 1979. The Eurasian strain is generally found in Europe and Asia, rather than North America.
Neither of the strains have ever proven contagious in humans. One of the genes inherited from the Eurasian strain has reportedly never been seen in humans. It codes for the neuraminidase enzyme — the N1 in H1N1 — which controls the expansion of the virus from infected cells.
“The new neuraminidase gene that came in from Eurasian swine is one we’ve never before seen circulating in humans,” said Rambaut. “That’s one of the reasons it’s spreading rapidly. Very few people will have any immunity to this particular combination, which is what gives the concern that this will be a pandemic rather than just a normal seasonal flu outbreak. It remains to be seen how much and to what extent there is existing immunity.”
In medical terms, the genetic origins of the virus may not matter. Whether it come solely from pigs rather than a mix of pigs, birds and humans doesn’t change its immunological novelty.
However, understanding the origins could eventually help scientists determine how the virus evolved and where it originally emerged.
The earliest cases occurred in the town of La Gloria in the Mexican state of Veracruz, not far from a large and notoriously unsanitary hog farm operated by Granjas Carroll, a subsidiary of giant American food company Smithfield Foods.
Vercruz residents and some journalists have alleged that the virus could have evolved in the farm’s pigs, then passed into humans through water or insects tainted by infected waste. Many researchers, including the authors of a report issued last year by the Pew Commission on Industrial Farm Animal Production, have warned that unsanitary conditions at industrial hog farms could prove a breeding ground for new forms of influenza.
The World Health Organization has sent inspectors to the Granjas Carroll farm. The results of the investigation have not been announced. Smithfield issued a press release on Saturday stating that “it has found no clinical signs or symptoms of the presence of swine influenza in the company’s swine herd or its employees at its joint ventures in Mexico.” The company declined further comment, though CEO Larry Pope told USA Today that “(The term) swine flu is a misnomer.”
Rambaut, Holmes and Salzberg declined to speculate on whether the new H1N1 virus evolved on a hog farm or specifically in the Granjas Carroll facility.
However, it seems likely that pigs were the original host.
“That’s a logical conclusion,” said Salzberger. “It was probably two different pigs, or one who got co-infected from others. The two strains mixed, and now you have a brand-new strain.”
“Presumably somewhere there was a pig infected with both forms. We don’t know where or when. It could have been circulating in this form for a while,” said Rambaut.
What comes next is anyone’s guess.
“Influenza virus mutates remarkably rapidly so there is no doubt that the virus will mutate and evolve in humans,” said Holmes. “Quite what this evolution will result in is difficult to tell.”
致命的、引發全球擔憂大流行的 H1N1 流感病毒是兩種常見的豬流感病毒的雜交品種,研究過這種疾病的科學家在星期二告訴 Wired.com 說。早先的報道稱其為豬、人和禽流感菌株的結合。
這一發現可能解決關于這種病毒性質的一些不確定性問題,但是有關它的起源和影響還有許多不明之處。
“這就是我們稱之為在兩種目前流行的豬流感病毒之間的重組物的東西 ”Edinborough 大學的病毒遺傳學家安德魯 拉姆鮑特說。 “任何人都在猜測為什么它在人類中出現。據我所知,以前還沒有在豬中見過它。”
拉姆鮑特分析了來自加利福尼亞州兩個感染兒童的病毒樣本的基因序列。樣本是由疾病控制和預防中心收集的,通過一個國際流感基因組數據庫提供給研究人員。
他的結論得到了賓夕法尼亞大學病毒演變專家埃迪 霍爾姆斯和馬里蘭大學生物信息學家史蒂芬 薩爾茨貝克的附和。兩者都查看過疾病預防和控制中心提供的序列。該中心還沒有就此發表評論,但是向科學家們公布的并且由 Wired.com 獲得的一份文件申明了他們的分析。
研究人員們認為,來自加利福尼亞州的樣本代表了與造成多達 150 名墨西哥人死亡,估計 1600 名墨西哥人進醫院治療,并且引起世界范圍內數百人感染,其中包括在美國至少 64 人感染的同樣的病毒菌株。然而,來自墨西哥的樣品尚未排序,類似性尚未確證。
在加利福尼亞州的樣本中發現其基因的這兩個菌株,屬于一般稱為北美豬流感和歐亞豬流感的流感系列。前者首次在 20 世紀 30 年代被描述過,后者在 1979 年被描述過。歐亞菌株一般在歐洲和亞洲發現,而不是北美。
這兩類菌株都未曾被證明過在人類中是傳染性的。其中一個從歐亞菌株遺傳的的基因據報告從未在人類中見過。它編碼為神經氨酸酶——H1N1 中的 N1,它控制病毒從感染細胞的擴展。
“這種來自歐亞豬的新的神經氨酸酶基因是一種我們從未見過在人類中流行的基因,”拉姆鮑特說。 “這是它迅速蔓延的原因之一。極少數人會對這種特定的組合有免疫力,它讓我們關注的是,這會是一個大流行,而不僅僅是通常的季節性流感暴發。現有的免疫性有多少以及達到多大的程度,還有待觀察。”
病毒的遺傳起源在醫療方面可能并不重要。不論它僅僅是來自豬還是來自豬、鳥類和人類的混合,都不改變其免疫新穎性。
然而,了解起源可能最終幫助科學家們確定病毒如何演變以及它最初是在哪里出現的。
最早的病例發生在墨西哥韋拉克魯斯州的拉格洛里亞鎮,離一個大的、人所周知的不衛生的養豬場不遠,這個養豬場由巨頭美國食品公司史密斯菲德食品公司的一家子公司格蘭加斯 卡羅爾公司所經營。
韋拉克魯斯的居民和一些記者聲稱,病毒可能是在農場的豬中演變的,然后通過受感染的廢物所污染的水或者昆蟲傳遞到人類。許多研究人員,其中包括去年通過佩尤產業家畜生產委員會發表一份報告的作者,已經警告過,產業養豬場的不衛生條件,可能被證明是新流感形式的一個溫床。
世界衛生組織已經派出檢查人員到格蘭加斯卡羅爾公司的農場。調查結果還沒有對外公布。史密斯菲德公司上周六發出的新聞稿聲稱,“在它在墨西哥的合資企業中,公司的豬畜群或者其雇員,沒有發現任何存在豬流感的臨床體狀或者癥候。”該公司拒絕作進一步的評論,盡管首席執行官拉里 珀布告訴《今日美國》說“豬流感(這個詞)是一個誤稱。”
拉姆鮑特、霍爾姆斯和薩爾茨貝克拒絕推測是否新的 H1N1 病毒是在養豬場或者具體是在格蘭加斯 卡羅爾公司的設施內演變的。
然而,似乎可能豬是最初的宿主。
“這是合乎邏輯的結論,” 薩爾茨貝克說。“這可能是兩種不同的豬,或者是一種從另一種得到并合感染的豬。兩種菌株混合,現在就有了一種全新的菌株。”
“大概某處有過一頭感染了兩種形式菌株的豬。我們不知道是在哪里或者是在什么時候。它可能已經以這種形式傳播了一段時間,” 拉姆鮑特說。
任何人都在猜測下一步出現什么。
“流感病毒變異非常迅速,所以毫無疑問,該病毒會在人類中發生變異和演化,”霍爾姆斯說。 “難以講這種演變完全會導致什么。”