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Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation
Author(s) -
Sun Yingjie,
Dong Luna,
Yu Shengqing,
Wang Xiaoxu,
Zheng Hang,
Zhang Pin,
Meng Chunchun,
Zhan Yuan,
Tan Lei,
Song Cuiping,
Qiu Xusheng,
Wang Guijun,
Liao Ying,
Ding Chan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600980r
Subject(s) - replication (statistics) , translation (biology) , host (biology) , virology , stress granule , viral replication , virus , newcastle disease , host factors , microbiology and biotechnology , disease , biology , genetics , medicine , gene , messenger rna , pathology
Mammalian cells respond to various environmental stressors to form stress granules (SGs) by arresting cyto‐plasmic mRNA, protein translation element, and RNA binding proteins. Virus‐induced SGs function in different ways, depending on the species of virus; however, the mechanism of SG regulation of virus replication is not well understood. In this study, Newcastle disease virus (NDV) triggered stable formation of bona fide SGs on HeLa cells through activating the protein kinase R (PKR)/eIF2α pathway. NDV‐induced SGs contained classic SG markers T‐cell internal antigen (TIA)‐1, Ras GTPase‐activating protein‐binding protein (G3BP)‐1, eukaryotic initiation factors, and small ribosomal subunit, which could be disassembled in the presence of cycloheximide. Treatment with nocodazole, a microtubule disruption drug, led to the formation of relatively small and circular granules, indicating that NDV infection induces canonical SGs. Furthermore, the role of SGs on NDV replication was investigated by knockdown of TIA‐1 and TIA‐1‐related (TIAR) protein, the 2 critical components involved in SG formation from the HeLa cells, followed by NDV infection. Results showed that depletion of TIA‐1 or TIAR inhibited viral protein synthesis, reduced extracellular virus yields, but increased global protein translation. FISH revealed that NDV‐induced SGs contained predominantly cellular mRNA rather than viral mRNA. Deletion of TIA‐1 or TIAR reduced NP mRNA levels in polysomes. These results demonstrate that NDV triggers stable formation of bona fide SGs, which benefit viral protein translation and virus replication by arresting cellular mRNA. —Sun, Y., Dong, L., Yu, S., Wang, X., Zheng, H., Zhang, P., Meng, C., Zhan, Y., Tan, L., Song, C., Qiu, X., Wang, G., Liao, Y., Ding, C. Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation. FASEB J . 31, 1337–1353 (2017) www.fasebj.org