Dengue virus infection induces formation of G3BP1 granules in human lung epithelial cells.
Cells reprogram ongoing translation in response to viral infection, resulting in formation of stress granules (SGs), while viruses have evolved a variety of strategies to antagonize the host SG response. Previous literature reported that in BHK-1 cells, infection with dengue virus (DENV) interfered with the SG formation. In the current study, we further investigated SG formation in human epithelial A549 cells by detecting subcellular localization of two SG hallmarks, TIA-1 and G3BP1. In response to DENV type 2 (DENV2) and type 3 (DENV3) infection, G3BP1, but not TIA-1, was recruited into cytoplasmic granules in some cells, and viral protein synthesis was significantly impaired in the G3BP1-granule-containing cells. Knockdown of G3BP1 significantly rescued the dsRNA-mediated suppression of DENV2 replication. Furthermore, our data showed that the phosphorylation of protein kinase regulated by dsRNA (PKR) and eIF2α, as well as accumulation of dsRNA, mainly occurred at the late stage of viral infection. This work revealed that in DENV-infected A549 cells, G3BP1 granules were assembled independently of TIA-1 and had a negative impact on viral replication. This extends our understanding of the antagonistic relationship between the SG response and dengue virus infection.
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China.
Jun
J
Xia
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China.
Xiaoyan
X
Chen
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China.
Feng
F
Xu
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China.
Yi
Y
Wang
Guangdong Inspection and Quarantine Technology Center, Guangzhou, 510080, China.
Yongxia
Y
Shi
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China.
Yuye
Y
Li
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. hejf@mail.sysu.edu.cn.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China. hejf@mail.sysu.edu.cn.
Junfang
J
He
Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. zhangp36@mail.sysu.edu.cn.|Key Laboratory of Tropical Diseases Control, Ministry of Education, Guangzhou, 510080, China. zhangp36@mail.sysu.edu.cn.
Ping
P
Zhang
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism / Q000821:virology; D004265:DNA Helicases; D003715:Dengue / Q000378:metabolism* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000821:virology; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D014779:Virus Replication
D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases