State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, China.
State Key Laboratory of Virology and Modern Virology Research Center, College of Life Sciences, Wuhan University, LuoJia Hill, Wuhan 430072, China.
Cell Rep. 2019 Nov 19;29(8):2229-2242.e4. doi: 10.1016/j.celrep.2019.10.052.
Many positive-strand RNA viruses remodel the endomembrane to form specialized replication organelles. However, knowledge regarding whether negative-strand RNA viruses take advantage of intracellular membranes for replication is limited. Here we show that a negative-strand RNA virus, human parainfluenza virus type 3 (HPIV3), remodels the endoplasmic reticulum (ER) membrane to form inclusion bodies (IBs), whereby the phosphoprotein (P) of HPIV3 recruits phosphatidylinositol 4-kinase beta (PI4KB) to IBs to generate PI4P, creating a PI4P-enriched microenvironment to promote HPIV3 replication. In addition, we find that human respiratory syncytial virus (HRSV) also takes advantage of the ER to form IBs and that these IBs are also enriched with PI4P. The nucleoprotein of HRSV recruits PI4KB to IBs. These results suggest that paramyxoviruses also exploit the host endomembrane to form IBs and that PI4KB is recruited by viral proteins to enrich IBs with PI4P to facilitate viral replication.
许多正链 RNA 病毒重塑内体膜以形成专门的复制细胞器。然而，关于负链 RNA 病毒是否利用细胞内膜进行复制的知识有限。在这里，我们表明，一种负链 RNA 病毒，人类副流感病毒 3 型（HPIV3），重塑内质网（ER）膜以形成包涵体（IBs），其中 HPIV3 的磷蛋白（P）将磷酸肌醇 4-激酶β（PI4KB）募集到 IBs 以产生 PI4P，从而创造富含 PI4P 的微环境以促进 HPIV3 复制。此外，我们发现人类呼吸道合胞病毒（HRSV）也利用 ER 形成 IBs，并且这些 IBs 也富含 PI4P。HRSV 的核蛋白将 PI4KB 募集到 IBs。这些结果表明副粘病毒也利用宿主内膜形成 IBs，并且病毒蛋白招募 PI4KB 以在 IBs 中富集 PI4P 以促进病毒复制。
