Inclusion bodies of human parainfluenza virus type 3 inhibit antiviral stress granule formation by shielding viral RNAs.
Inclusion bodies of human parainfluenza virus type 3 inhibit antiviral stress granule formation by shielding viral RNAs.
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人副流感病毒3型包涵体通过屏蔽病毒RNA抑制抗病毒应激颗粒形成
DOI：
10.1371/journal.ppat.1006948
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发表时间：
2018-03
期刊：
影响因子：
6.7
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Hu Z;Wang Y;Tang Q;Yang X;Qin Y;Chen M
病毒入侵触发宿主抗病毒反应的激活。除了先天免疫反应外，应激颗粒（SG）还作为一种额外的防御反应来对抗病毒复制。然而，许多病毒已经进化出各种策略来抑制SG形成以促进其自身复制。在这里，我们表明，来自人副流感病毒3型（HPIV 3）感染的病毒mRNA诱导SG形成的eIF 2 α磷酸化和PKR依赖的方式，其中病毒mRNA被隔离和病毒复制被抑制的干扰素信号通路无关。此外，我们还发现HPIV 3的核蛋白（N）和磷蛋白（P）相互作用形成的包涵体（IB）与SG抑制相关。此外，P与NL 478 A（N的点突变体，其不能与P形成IB）或NΔN10（N的N-末端10个氨基酸缺失，其可以与P形成IB但不能合成或屏蔽病毒RNA）的共表达未能抑制SG形成，这表明SG形成的抑制也与IB合成和屏蔽病毒RNA的能力相关。因此，我们提供了一个模型，使病毒IBs逃避抗病毒效果的SG隐藏自己的新合成的病毒RNA，并提供新的见解IBs在病毒复制中的新兴作用。人副流感病毒3型（HPIV 3）是引起婴儿和儿童肺炎和支气管炎等急性呼吸道疾病的主要原因之一。病毒入侵激活细胞应激反应。这些反应之一是形成抵抗病毒复制的SG。然而，许多病毒已经进化出各种策略来抑制SG形成，从而促进它们自身的复制。我们试图确定HPIV 3是否（以及如何）调节SG形成以促进其复制，并发现HPIV 3的病毒信使RNA（mRNA）触发感染细胞中的SG形成。随着感染后时间的增加，含有SG的细胞数量也增加。为了逃避这种反应，HPIV 3形成了IB来屏蔽病毒RNA，从而阻止SG的形成，并允许病毒复制和存活-并可能入侵其他细胞。
Viral invasion triggers the activation of the host antiviral response. Besides the innate immune response, stress granules (SGs) also act as an additional defense response to combat viral replication. However, many viruses have evolved various strategies to suppress SG formation to facilitate their own replication. Here, we show that viral mRNAs derived from human parainfluenza virus type 3 (HPIV3) infection induce SG formation in an eIF2α phosphorylation- and PKR-dependent manner in which viral mRNAs are sequestered and viral replication is inhibited independent of the interferon signaling pathway. Furthermore, we found that inclusion body (IB) formation by the interaction of the nucleoprotein (N) and phosphoprotein (P) of HPIV3 correlated with SG suppression. In addition, co-expression of P with NL478A (a point mutant of N, which is unable to form IBs with P) or with NΔN10 (lacking N-terminal 10 amino acids of N, which could form IBs with P but was unable to synthesize or shield viral RNAs) failed to inhibit SG formation, suggesting that inhibition of SG formation also correlates with the capacity of IBs to synthesize and shield viral RNAs. Therefore, we provide a model whereby viral IBs escape the antiviral effect of SGs by concealing their own newly synthesized viral RNAs and offer new insights into the emerging role of IBs in viral replication. Human parainfluenza virus type 3 (HPIV3) is one of the major causes of acute respiratory tract diseases such as pneumonia and bronchitis in infants and children. Virus invasion activates cellular stress responses. One of these responses is the formation of SGs which counteract viral replication. However, many viruses have evolved various strategies to suppress SG formation, thus facilitating their own replication. We sought to determine if (and how) HPIV3 modulates SG formation to facilitate its replication and found that the viral messenger RNAs (mRNAs) of HPIV3 trigger SG formation in infected cells. As time increased post-infection, the number of cells containing SGs increased as well. To escape this response, HPIV3 forms IBs that shield viral RNAs, thereby preventing SG formation and allowing the virus to replicate and survive—and potentially invade other cells.
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DOI：
10.1073/pnas.0703348104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Emara, Mohamed M.;Brinton, Margo A.
通讯作者：
Brinton, Margo A.
影响因子：
11.4
作者：
Iseni, F;Garcin, D;Kolakofsky, D
通讯作者：
Kolakofsky, D
影响因子：
30.5
作者：
Kawai, T;Takahashi, K;Akira, S
通讯作者：
Akira, S
影响因子：
5.4
作者：
Dinh, Phat X.;Beura, Lalit K.;Pattnaik, Asit K.
通讯作者：
Pattnaik, Asit K.
影响因子：
3.7
作者：
Durbin, AP;Siew, JW;Collins, PL
通讯作者：
Collins, PL