Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability.
Cell-Based Influenza A/H1N1pdm09 Vaccine Viruses Containing Chimeric Hemagglutinin with Improved Membrane Fusion Ability.
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DOI：
10.3390/vaccines8030458
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发表时间：
2020-08-19
期刊：
影响因子：
7.8
通讯作者：
Morikawa Y
中科院分区：
文献类型：
--
作者：
Kawahara M;Wada T;Momose F;Nobusawa E;Morikawa Y
H1N1流感大流行性疫苗是由A/加州/07/09（Cal）病毒和众所周知的高产A/波多黎各/8/34（PR 8）病毒通过经典重配和反向遗传学（RG）在鸡蛋中开发的。以往的研究表明，钙衍生的嵌合血凝素（HA）和神经氨酸酶（NA）提高病毒产量。然而，H1N1大流行性病毒的细胞疫苗研究较少。含有Cal衍生的嵌合HA和NA的RG病毒可以在表达α 2，6-唾液酸转移酶（MDCK-SIAT 1）的Madin-Darby犬肾细胞中被拯救。分析病毒生长动力学和嵌合HA和NA特性。我们试图产生含有Cal衍生的嵌合HA和NA的各种RG病毒，但其中一半不能在MDCK-SIAT 1细胞中被拯救。当Cal HA病毒RNA的3′-和5′-末端区域被PR 8 HA的相应区域替换时，RG病毒被拯救。我们的结果在很大程度上与以前的研究一致，其中N-和C-末端嵌合HA略微提高了病毒产量。重要的是，与Cal HA相比，嵌合HA在更宽的pH范围内显示出细胞融合能力，这可能是由于HA的跨膜区中的氨基酸取代。具有高病毒产量的拯救的RG病毒具有能够在更宽范围的pH下进行细胞融合的嵌合HA。
The H1N1 influenza pandemic vaccine has been developed from the A/California/07/09 (Cal) virus and the well-known high-yield A/Puerto Rico/8/34 (PR8) virus by classical reassortment and reverse genetics (RG) in eggs. Previous studies have suggested that Cal-derived chimeric hemagglutinin (HA) and neuraminidase (NA) improve virus yields. However, the cell-based vaccine of the H1N1 pandemic virus has been less investigated. RG viruses that contained Cal-derived chimeric HA and NA could be rescued in Madin–Darby canine kidney cells that expressed α2,6-sialyltransferase (MDCK-SIAT1). The viral growth kinetics and chimeric HA and NA properties were analyzed. We attempted to generate various RG viruses that contained Cal-derived chimeric HA and NA, but half of them could not be rescued in MDCK-SIAT1 cells. When both the 3′- and 5′-terminal regions of Cal HA viral RNA were replaced with the corresponding regions of PR8 HA, the RG viruses were rescued. Our results were largely consistent with those of previous studies, in which the N- and C-terminal chimeric HA slightly improved virus yield. Importantly, the chimeric HA, compared to Cal HA, showed cell fusion ability at a broader pH range, likely due to amino acid substitutions in the transmembrane region of HA. The rescued RG virus with high virus yield harbored the chimeric HA capable of cell fusion at a broader range of pH.
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鸟类流感病毒中神经氨酸酶茎缺失的出现和遗传变异。
影响因子：
3.7
作者：
Li J;Zu Dohna H;Cardona CJ;Miller J;Carpenter TE
通讯作者：
Carpenter TE
影响因子：
3.5
作者：
Feshchenko E;Rhodes DG;Felberbaum R;McPherson C;Rininger JA;Post P;Cox MM
通讯作者：
Cox MM
影响因子：
5.5
作者：
Medina, Julie;Boukhebza, Houda;Moste, Catherine
通讯作者：
Moste, Catherine
DOI：
10.1073/pnas.84.22.8140
发表时间：
1987-11-01
影响因子：
11.1
作者：
HSU, MT;PARVIN, JD;PALESE, P
通讯作者：
PALESE, P
DOI：
10.1038/nrmicro3367
发表时间：
2015-01
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Eisfeld AJ;Neumann G;Kawaoka Y
通讯作者：
Kawaoka Y