禽流感病毒 H7N9 的致病機理為什麼現在才被發現？這個發現意味著什麼？

01-28

我國研究人員找到人感染H7N9病毒致病機理
不懂病毒學，不太明白髮現一種病毒的致病機理是什麼工作量，以及意味著什麼，希望聽聽相關研究人員的科普

謝邀。拋磚引玉。

微生物所自己的新聞：微生物所在H7N9病毒致病基因方面取得研究進展----中國科學院微生物研究所

原文鏈接：Assessment of the internal genes of influenza A (H7N9) virus contributing to the high pathogenicity in mice

原文標題：Assessment of the internal genes of influenza A (H7N9) virus contributing to the high pathogenicity in mice

原文摘要：Abstract

The recently identified H7N9 influenza A virus has caused severe economic losses and worldwide public concern. Genetic analysis indicates that its six internal genes all

originated from H9N2 viruses. However, the H7N9 virus is more highly pathogenic in humans than H9N2, which suggests that the internal genes of H7N9 have mutated.

H7N9病毒獨立很強，但是其6個基因片段來源於H9N2，而這個病毒卻不怎麼厲害，說明H7N9病毒突變了。

那麼問題來了，是怎麼突變的呢？

To analyze which H7N9 virus internal genes contribute to its high pathogenicity, a series of reassortants were generated by reverse genetics, each containing a single internal gene of the typical A/Anhui/1/2013(H7N9) virus in the genetic background of the A/chicken/Shandong/lx1023/2007(H9N2) virus.

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reverse genetics/反向遺傳學：可以參考 @子小的回答只有病毒 DNA 或 RNA 的情況下是否能複製完整的病毒出來？ - 生物學

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Their replication ability, polymerase activity, and pathogenicity were then evaluated in vitro and in vivo.

要分析為什麼？作者把H7N9和H9N2病毒的8個基因片段進行一系列的重新排列組合。來分析各個組合出來的病毒的複製能力、聚合酶的活性和致病性。

These recombinants displayed high genetic compatibility, and the H7N9-derived PB2, M, and NP genes were identified as the virulence genes for the reassortants in mice. Further investigation confirmed PB2-K627 is critical for the high pathogenicity of the H7N9 virus and the reassortant containing the H7N9-derived PB2 segment (H9N2-AH/PB2).

這些組合出來的病毒兼容性很好，說明重組病毒可以比較好的活著。進一步還發現PB2基因的K627對於H7N9的高致病性很重要。

Notably, the H7N9-derived PB2 gene displayed a greater compatibility with the H9N2 genome than that of H7N9, endowing the H9N2-AH/PB2 reassortant with greater viability and virulence than the parental H7N9 virus. In addition, the H7N9 virus, with the exception of the H9N2 reassortants, could effectively replicate in human A549 cells. Our results indicate that PB2, M, and NP are the key virulence genes, together with the surface HA and NA proteins, contributing to the high infectivity of the H7N9 virus in humans.

而且，H7N9的PB2與H9N2的其他基因的相容性更好。表現在活力和毒力比H7N9還強。但是H7N9能在人的肺癌細胞（A549）中很好的複製【因為以前認為禽流感不能感染人，但是這種重新組合之後導致H7N9爆發是能夠在傳播到人的】。

作者總結了：流感的PB2、M、NP是主要的毒力基因，而且與病毒表面的HA和NA蛋白【一個用來進入細胞，一個用來離開細胞】一起都導致了H7N9對人的高度感染性。

P.S. 微生物所前期研究已經說明過了，HA的一個突變導致病毒結合的受體更類似於人而不類似於禽類。

不過這個問題還是 @譚大毛來回答比較合適。