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本文介绍了美国威斯康星大学麦迪逊分校病毒学教授河冈义裕(Yoshihiro Kawaoka)科研团队关于禽流感在人型模式动物雪貂之间传染的研究。团队用反向遗传学方法把H5N1和H1N1病毒重组成新的H5N1病毒。这种重组的禽-人流感病毒共分两类,第1类是VN1203(H5N1)+PR8(H1N1),其中HA、HN来自VN1203,其余6个基因来自PR8;第2类是VN1203+CA04(H1N1),HA来自VN1203,其余7个基因来自CA04。团队用采用GeneMorph Ⅱ kit(Stratagene)试剂盒诱导HA发生一系列突变,其中2联突变N224K/Q226L可以使重组H5N1病毒特异性结合人型受体并且感染人类呼吸道组织切片,3联突变N158D/N224K/Q226L可以使H5N1在雪貂之间传染,4联突变N158D/N224K/Q226L/T381I的传染性更强。2联突变N224K/Q226L对于H5N1由特异性感染禽类转变为特异性感染人型模式受体和动物起到了关键作用,N158D突变进一步增加了H5特定区域去糖基化的作用,增加了H5对人型受体的传染能力,T381I突变提高了H5在人型受体环境中的稳定性以及与受体细胞的融合性,因而4联突变N158D/N224K/Q226L/T381I的H5表现出最强的传染性。团队发出警告,在自然界中,N158点位上去糖基化的突变已经广泛发生,现在只剩下N224、Q226、或者T381点位还在防止H5N1向人类传染,但是这2个、或者3个点位还能坚持多久不发生突变?
This article describes research by Yoshihiro Kawaoka, a professor of virology at the University of Wisconsin-Madison, on the spread of bird flu among humanoid ferrets. The team re-engineered the H5N1 and H1N1 viruses into a new H5N1 virus using reverse genetics. This recombinant avian-human influenza virus is divided into two categories, the first is VN1203 (H5N1) + PR8 (H1N1), wherein HA, HN are from VN1203 and the remaining 6 are from PR8; the second is VN1203 + CA04 H1N1), HA is from VN1203 and the remaining 7 genes are from CA04. The team used a GeneMorph II kit (Stratagene) kit to induce a series of mutations in HA. Two of the mutations, N224K / Q226L, allowed the recombinant H5N1 virus to specifically bind to human receptors and infect human respiratory tissue sections. The triple mutant N158D / N224K / Q226L allows H5N1 to be transmitted between ferrets, and the 4-mer mutant N158D / N224K / Q226L / T381I is more contagious. 2 Mutagenesis N224K / Q226L plays a key role in the conversion of H5N1 from specifically infected poultry to specifically infect human-type receptors and animals, and the N158D mutation further increases the deglycosylation of specific regions of H5 and increases the effect of H5 on human T381I mutation increased the stability of H5 in the human-type receptor environment and the fusion with the recipient cells, and thus the H5 of the 4-mutated N158D / N224K / Q226L / T381I showed the strongest infection Sex. The team warned that mutations in the N158 glycosylation site have been widespread in nature, leaving only N224, Q226, or T381 sites still preventing H5N1 from infecting humans, but these 2 or 3 spots Bit can insist on how long no mutation?