甲型流感為急性呼吸道傳染病，其病原體是一種新型的甲型H1N1流感病毒,，在人群中傳播,。自2009年開始，甲型H1N1流感在全球范圍內(nèi)大規(guī)模流 行。2010年8月,，世衛(wèi)組織宣布甲型H1N1流感大流行期已經(jīng)結(jié)束,。2012年我國甲型H1N1流感病例超過300例，由于流感病毒經(jīng)常發(fā)生抗原漂移,， 因此經(jīng)常發(fā)生規(guī)模大小不等的暴發(fā)流行,。
中國科學(xué)院動物研究所何宏軒研究員領(lǐng)導(dǎo)的野生動物疫病研究組2009年在《科學(xué)通報》上發(fā)表了甲型H1N1北美毒株特征（Chinese SciBull,2009），證明了甲型H1N1流感的變異和進(jìn)化,，對于人類呈現(xiàn)高親和力,、低致病性、不具有高致病性流感病毒的特性,、對神經(jīng)氨酸酶抑制劑類藥物敏感,，但對 金剛烷胺類藥物具有抗性等4大特征。近期又對甲型流感爆發(fā)以來H1N1病毒所有片段進(jìn)行了選擇壓力分析,，結(jié)果發(fā)現(xiàn)除NS片段外其余7個片段的編碼區(qū)都呈現(xiàn) 明顯的負(fù)選擇壓力,，表明它們對人是比較適應(yīng)的。
NS片段是流感病毒的最小片段,，其編碼NS1和NS2兩個蛋白,，分析發(fā)現(xiàn)NS1片段也呈現(xiàn)負(fù)選擇壓力，而NS2片段則在流感剛剛爆發(fā)的4月呈現(xiàn)出明 顯的正選擇壓力,，因此認(rèn)為NS片段極有可能在以前感染人H1N1病毒中從未出現(xiàn)過,，在2009H1N1病毒中出現(xiàn)對于甲型流感進(jìn)入人體并導(dǎo)致疫情爆發(fā)可能 具有一定的作用，而另一個不同尋常之處在于2009年8月的病毒NS2片段再次表現(xiàn)出明顯的正選擇壓力,，這與一般的病毒跨宿主傳播的遺傳進(jìn)化理論不符,。對 于這一奇怪現(xiàn)象，認(rèn)為這與7月份以后甲流病毒傳播速度和傳播范圍的急速擴(kuò)大有關(guān)系,，病毒接觸到的群體數(shù)量,、群體多樣性都大為增加，因此病毒在進(jìn)化過程中再 一次受到了正選擇壓力,，進(jìn)一步表明NS片段是2009年前后重組到人流感病毒基因組的可能性,。
NS片段的遺傳突變網(wǎng)絡(luò)分析，甲型流感病毒自4月份出現(xiàn)以來,，就以兩個基礎(chǔ)的突變型（G1型,123V 和G2型,123I）為原點進(jìn)行進(jìn)化,，這個變異的位點處于NS1的編碼區(qū)。出現(xiàn)這一現(xiàn)象有兩種可能,，一是在病毒最初傳播到人宿主時就是以兩個突變型的形式先后傳入的,，該突 變可能在甲流未傳入人的時候就已經(jīng)出現(xiàn)，因為這兩個基本突變性出現(xiàn)的時間都非常早,，同時又分別都有大量的感染群體和后期進(jìn)化毒株的出現(xiàn),；二是病毒先以G1 或G2中的一種進(jìn)入人體,，而后另外一種由原始突變型進(jìn)化而來，但顯然該位點的突變使病毒獲得了明顯的感染傳播優(yōu)勢,，在短期內(nèi)形成了龐大感染群體,。
綜上所述，認(rèn)為NS片段是這次甲型流感暴發(fā)過程中的一個極為特殊的片段,，很有可能對甲流爆發(fā)以及蔓延起到了重要的作用,。這一研究結(jié)果發(fā)表在《PLOS綜合》雜志上,。該項目獲得了國家自然科學(xué)基金青年基金,，中科院知識創(chuàng)新工程等項目的支持。（生物谷Bioon.com）
DOI：10.1371/journal.pone.0025808
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Reassortant H9N2 Influenza Viruses Containing H5N1-Like PB1 Genes Isolated from Black-Billed Magpies in Southern China
Guoying Dong, Cong Xu, Chengmin Wang, Bin Wu, Jing Luo, Hong Zhang, Dale Louis Nolte
H9N2 influenza A viruses have become endemic in different types of terrestrial poultry and wild birds in Asia, and are occasionally transmitted to humans and pigs. To evaluate the role of black-billed magpies (Pica pica) in the evolution of influenza A virus, we conducted two epidemic surveys on avian influenza viruses in wild black-billed magpies in Guangxi, China in 2005 and characterized three isolated black-billed magpie H9N2 viruses (BbM viruses). Phylogenetic analysis indicated that three BbM viruses were almost identical with 99.7 to 100% nucleotide homology in their whole genomes, and were reassortants containing BJ94-like (Ck/BJ/1/94) HA, NA, M, and NS genes, SH/F/98-like (Ck/SH/F/98) PB2, PA, and NP genes, and H5N1-like (Ck/YN/1252/03, clade 1) PB1 genes. Genetic analysis showed that BbM viruses were most likely the result of multiple reassortments between co-circulating H9N2-like and H5N1-like viruses, and were genetically different from other H9N2 viruses because of the existence of H5N1-like PB1 genes. Genotypical analysis revealed that BbM viruses evolved from diverse sources and belonged to a novel genotype (B46) discovered in our recent study. Molecular analysis suggested that BbM viruses were likely low pathogenic reassortants. However, results of our pathogenicity study demonstrated that BbM viruses replicated efficiently in chickens and a mammalian mouse model but were not lethal for infected chickens and mice. Antigenic analysis showed that BbM viruses were antigenic heterologous with the H9N2 vaccine strain. Our study is probably the first report to document and characterize H9N2 influenza viruses isolated from black-billed magpies in southern China. Our results suggest that black-billed magpies were susceptible to H9N2 influenza viruses, which raise concerns over possible transmissions of reassortant H9N2 viruses among poultry and wild birds.
