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 N_L478A (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.

病毒入侵会触发宿主抗病毒反应的激活。除先天免疫反应外，应激颗粒（SGs​​）还可作为对抗病毒复制的额外防御反应。但是，许多病毒已经进化出各种策略来抑制SG的形成，以促进其自身的复制。在这里，我们显示了源自人类副流感病毒3型（HPIV3）感染的病毒mRNA以eIF2α磷酸化和PKR依赖性方式诱导SG形成，其中病毒mRNA被隔离并且病毒复制被独立于干扰素信号传导途径抑制。此外，我们发现HPIV3的核蛋白（N）和磷蛋白（P）相互作用形成包涵体（IB）与SG抑制有关。另外，P与N _L478A共表达（N的点突变体，不能与P形成IBs）或NΔN10（缺少N的N末端10个氨基酸，可以与P形成IBs，但不能合成或屏蔽病毒RNA）无法抑制SG IB的形成，这表明对SG形成的抑制也与IB合成和屏蔽病毒RNA的能力有关。因此，我们提供了一个模型，其中病毒IB通过隐藏自身新合成的病毒RNA逃脱了SG的抗病毒作用，并为IB在病毒复制中的新兴作用提供了新见解。