Recombinant human parainfluenza virus type 2 with mutations in V that permit cellular interferon signaling are not attenuated in non-human primates.
Recombinant human parainfluenza virus type 2 with mutations in V that permit cellular interferon signaling are not attenuated in non-human primates.
复制标题
DOI：
10.1016/j.virol.2010.07.011
复制
发表时间：
2010-10-10
期刊：
影响因子：
3.7
通讯作者：
Schmidt AC
中科院分区：
文献类型：
--
作者：
Schaap-Nutt A;D'Angelo C;Amaro-Carambot E;Nolan SM;Davis S;Wise SM;Higgins C;Bradley K;Kim O;Mayor R;Skiadopoulos MH;Collins PL;Murphy BR;Schmidt AC
HPIV 2 V蛋白抑制I型干扰素（IFN）诱导和信号传导。为了操纵V蛋白，其编码序列与聚合酶相关磷蛋白（P）的编码序列重叠，而不改变P蛋白，我们产生了一种HPIV 2病毒，其中P和V由不同的基因表达（rHPIV 2-P+V）。rHPIV 2-P+V在体外和非人灵长类动物中的复制与HPIV 2-WT相似。通过在V蛋白中引入两个单独的突变来修饰HPIV 2-P+V，以产生rHPIV 2-L101 E/L102 E和rHPIV 2-Δ122-127。与HPIV 2-WT相反，两种突变病毒都不能降解STAT 2，使病毒感染的细胞对IFN敏感。突变体和HPIV 2-WT均未在感染细胞中诱导显著量的IFN-β。令人惊讶的是，在两种非人灵长类动物中，rHPIV 2-L101 E/L102 E和rHPIV 2-Δ122-127均未减毒。这表明HPIV 2抑制IFN信号传导的能力的丧失不足以减弱体内病毒复制，只要IFN诱导仍然被抑制。
The HPIV2 V protein inhibits type I interferon (IFN) induction and signaling. To manipulate the V protein, whose coding sequence overlaps that of the polymerase-associated phosphoprotein (P), without altering the P protein, we generated an HPIV2 virus in which P and V are expressed from separate genes (rHPIV2-P+V). rHPIV2-P+V replicated like HPIV2-WT in vitro and in non-human primates. HPIV2-P+V was modified by introducing two separate mutations into the V protein to create rHPIV2-L101E/L102E and rHPIV2-Δ122–127. In contrast to HPIV2-WT, both mutant viruses were unable to degrade STAT2, leaving virus-infected cells susceptible to IFN. Neither mutant, nor HPIV2-WT, induced significant amounts of IFN-β in infected cells. Surprisingly, neither rHPIV2-L101E/L102E nor rHPIV2-Δ122–127 was attenuated in two species of non-human primates. This indicates that loss of HPIV2's ability to inhibit IFN signaling is insufficient to attenuate virus replication in vivo as long as IFN induction is still inhibited.
登录
查看更多内容
影响因子：
5.5
作者：
Bartlett, EJ;Amaro-Carambot, E;Skiadopoulos, MH
通讯作者：
Skiadopoulos, MH
猿猴病毒 5 的 V 蛋白通过靶向 STAT1 进行蛋白酶体介导的降解来抑制干扰素信号传导
影响因子：
5.4
作者：
Didcock, L;Young, DF;Randall, RE
通讯作者：
Randall, RE
影响因子：
6.4
作者：
Belshe, RB;Newman, FK;Anderson, E
通讯作者：
Anderson, E
影响因子：
3.7
作者：
Curran J;de Melo M;Moyer S;Kolakofsky D
通讯作者：
Kolakofsky D
影响因子：
3.7
作者：
He, B;Paterson, RG;Lamb, RA
通讯作者：
Lamb, RA