承載2009/H1N1基因的H5N1複合病毒，可透過飛沫傳染豚鼠

【縛雞之見】

這是20200401林保華〈美國戰疫 百國聯軍須向習索真相〉文章所指的（類似）文章：以逆向基因工程重組H5N1與H1N1病毒，多達127組。

承載2009/H1N1基因的H5N1複合病毒，可透過飛沫傳染豚鼠

https://science.sciencemag.org/content/340/6139/1459

H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet    Ying Zhang¹ et al ＠Science 20130621  Taimocracy翻譯

Science  21 Jun 2013:
Vol. 340, Issue 6139, pp. 1459-1463
DOI: 10.1126/science.1229455

Influencing Influenza

Currently, there is anxiety that the avian H5N1 influenza virus will reassort with the highly transmissible and epidemic H1N1 subtype to trigger a virulent human pandemic. Y. Zhang et al. (p. 1459, published online 2 May) used reverse genetics to make all possible reassortants between a virulent bird H5N1 with genes from a human pandemic H1N1.  Virulence was tested in mice and transmissibility was tested between guinea pigs, which have both avian- and human-like airway influenza virus receptors.  To assess what is happening to the receptor-ligand interactions as a result of these mutations, W. Zhang et al. (p. 1463, published online 2 May) probed the structure of both wild-type and mutant hemagglutinin of H5 in complex with analogs of the avian and human receptor types.  Certain mutations in the receptor-binding site changed binding affinity.

當前，人們擔心禽類H5N1流感病毒將與高度傳播和流行的H1N1亞型重新組合，從而引發致命的人類大流行。（Y. Zhang等，第1459頁，5月2日網上發布）使用逆向基因工程，使強毒禽類H5N1與人類大流行H1N1的基因之間發生了所有可能的重配。在小鼠中測試了毒性，並在豚鼠之間測試了它們的傳播性，豚鼠同時具有禽類和人類呼吸道流感病毒受體。為評估這些突變導致受體—配體相互作用發生了什麼，（W.Zhang等，第1463頁，5月2日網上發布）探討了H5的野生型和突變型血凝素與禽類和人類受體類型類似物的結構。受體結合位點的某些突變改變了結合親和力。

Abstract

In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts.  H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus.  We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor.  Transmission studies showed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them.  Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors.  Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.

過去，禽流感病毒通過與中間牲畜宿主中的哺乳動物感染性病毒重新配對，從而越過物種壁壘觸發人類大流行。 H5N1病毒能夠感染豬，其中一些對哺乳動物α-2,6-型唾液酸氣道受體具有親和力。使用反向遺傳學，我們系統地在H5N1鴨分離株和高度可傳播的人類感染H1N1病毒之間創建了127種重組病毒，這些分離株專門保留了其血凝素（HA）基因。我們測試了小鼠中重組蛋白的毒性，將其作為人類毒性的相關因素，並測試了豚鼠的傳播能力，豚鼠具有禽類和哺乳動物氣道受體。傳播研究表明，編碼酸性聚合酶和非結構蛋白的H1N1病毒基因使H5N1病毒可通過豚鼠之間的呼吸道飛沫傳播而不會殺死它們。進一步的實驗還牽涉到其他H1N1基因在哺乳動物向哺乳動物的傳播中的增強，包括編碼核蛋白，神經氨酸酶和基質的基因，以及H5 HA中的突變，這些突變可改善對類人氣道受體的親和力。因此，禽類H5N1亞型病毒在當前農業環境中確實有潛力透過重組而獲得哺乳動物的可傳播性。