Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis

The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between mu...

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Published inmBio Vol. 10; no. 3
Main Authors Fritzlar, Svenja, Aktepe, Turgut E, Chao, Yi-Wei, Kenney, Nathan D, McAllaster, Michael R, Wilen, Craig B, White, Peter A, Mackenzie, Jason M
Format Journal Article
LanguageEnglish
Published United States American Society for Microbiology 18.06.2019
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Abstract The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication. Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
AbstractList Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset. The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication. IMPORTANCE Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
ABSTRACT The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication. IMPORTANCE Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset. The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication.
The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular homeostasis. However, many viruses manipulate this response for their own advantage. In this study, we investigated the association between murine norovirus (MNV) infection and the ISR and demonstrate that MNV regulates the ISR by activating and recruiting key ISR host factors. We observed that during MNV infection, there is a progressive increase in phosphorylated eukaryotic initiation factor 2α (p-eIF2α), resulting in the suppression of host translation, and yet MNV translation still progresses under these conditions. Interestingly, the shutoff of host translation also impacts the translation of key signaling cytokines such as beta interferon, interleukin-6, and tumor necrosis factor alpha. Our subsequent analyses revealed that the phosphorylation of eIF2α was mediated via protein kinase R (PKR), but further investigation revealed that PKR activation, phosphorylation of eIF2α, and translational arrest were uncoupled during infection. We further observed that stress granules (SGs) are not induced during MNV infection and that MNV can restrict SG nucleation and formation. We observed that MNV recruited the key SG nucleating protein G3BP1 to its replication sites and intriguingly the silencing of G3BP1 negatively impacts MNV replication. Thus, it appears that MNV utilizes G3BP1 to enhance replication but equally to prevent SG formation, suggesting an anti-MNV property of SGs. Overall, this study highlights MNV manipulation of SGs, PKR, and translational control to regulate cytokine translation and to promote viral replication. Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess various defense mechanisms to detect, destroy, and clear infecting viruses, as well as signal to neighboring cells to inform them of the imminent threat. In this study, we demonstrate that the murine norovirus (MNV) infection stalls host protein translation and the production of antiviral and proinflammatory cytokines. However, virus replication and protein translation still ensue. We show that MNV further prevents the formation of cytoplasmic RNA granules, called stress granules (SGs), by recruiting the key host protein G3BP1 to the MNV replication complex, a recruitment that is crucial to establishing and maintaining virus replication. Thus, MNV promotes immune evasion of the virus by altering protein translation. Together, this evasion strategy delays innate immune responses to MNV infection and accelerates disease onset.
Author McAllaster, Michael R
Aktepe, Turgut E
White, Peter A
Kenney, Nathan D
Wilen, Craig B
Fritzlar, Svenja
Chao, Yi-Wei
Mackenzie, Jason M
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Cites_doi 10.7717/peerj.798
10.3389/fimmu.2017.00959
10.3201/eid1701.091101p1
10.1093/infdis/jix045
10.4049/jimmunol.1700384
10.1091/mbc.e06-04-0318
10.1128/mBio.00668-17
10.1096/fj.11-196915
10.1074/jbc.M412882200
10.1038/sj.cdd.4401833
10.1002/wrna.1162
10.1038/ni1584
10.1007/978-3-662-09889-9_3
10.1128/JVI.00600-09
10.1096/fj.10-168799
10.1093/emboj/cdg251
10.2741/2692
10.1586/erv.12.78
10.1126/science.1257147
10.1093/infdis/170.1.34
10.1083/jcb.147.7.1431
10.1128/JVI.02220-10
10.1128/JVI.78.16.8455-8467.2004
10.1016/S0021-9258(18)33352-0
10.1371/journal.pmed.1001807
10.1371/journal.pbio.0020432
10.1128/jvi.54.2.643-645.1985
10.1091/mbc.e05-02-0124
10.1073/pnas.0703348104
10.1074/jbc.M709563200
10.1016/j.tcb.2015.02.001
10.1371/journal.ppat.1000108
10.1126/science.1077905
10.1186/1743-422X-3-33
10.1091/mbc.01-05-0221
10.1016/S1074-7613(00)00014-5
10.1128/JVI.05784-11
10.3201/eid1908.130465
10.1086/657087
10.1016/0003-9861(87)90622-9
10.1074/jbc.M114.550657
10.1016/j.chom.2007.08.006
10.1074/mcp.M116.062448
10.1371/journal.ppat.1002413
10.1038/nrm1618
10.1086/341408
10.1128/JVI.02138-16
10.1128/jvi.61.8.2480-2488.1987
10.1093/infdis/119.6.668
10.1128/JVI.00260-10
10.3389/fmicb.2012.00092
10.1099/vir.0.005629-0
10.1093/cid/ciq163
10.1126/science.aaf5211
10.1016/j.virol.2012.11.017
10.1128/jvi.62.11.4216-4223.1988
10.1038/sj.embor.7400510
10.1016/j.virol.2010.06.047
10.1128/JVI.78.16.8582-8592.2004
10.1016/j.neulet.2006.09.074
10.1056/NEJMoa1101245
10.1126/science.aaf1220
10.1083/jcb.200512082
10.7554/eLife.00498
10.1128/JVI.00647-16
10.1371/journal.pone.0038723
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Issue 3
Keywords eIF2α
stress granules
protein translation
mouse norovirus
integrated stress response
protein kinase R
Language English
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This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
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S.F., T.E.A., and J.M.M. contributed equally to this work. S.F. and T.E.A. are joint authors.
Present address: Svenja Fritzlar, Department of Microbiology, Biomedical Discovery Unit, Monash University, Melbourne, Victoria, Australia.
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References e_1_3_2_26_2
e_1_3_2_49_2
e_1_3_2_28_2
e_1_3_2_41_2
e_1_3_2_64_2
e_1_3_2_20_2
e_1_3_2_43_2
e_1_3_2_62_2
e_1_3_2_22_2
e_1_3_2_45_2
e_1_3_2_68_2
e_1_3_2_24_2
e_1_3_2_47_2
e_1_3_2_66_2
e_1_3_2_60_2
e_1_3_2_9_2
e_1_3_2_16_2
e_1_3_2_37_2
e_1_3_2_7_2
e_1_3_2_18_2
e_1_3_2_39_2
e_1_3_2_54_2
e_1_3_2_10_2
e_1_3_2_31_2
e_1_3_2_52_2
e_1_3_2_5_2
e_1_3_2_12_2
e_1_3_2_33_2
e_1_3_2_58_2
e_1_3_2_3_2
e_1_3_2_14_2
e_1_3_2_35_2
e_1_3_2_56_2
e_1_3_2_50_2
e_1_3_2_27_2
e_1_3_2_48_2
e_1_3_2_29_2
e_1_3_2_40_2
e_1_3_2_65_2
e_1_3_2_21_2
e_1_3_2_42_2
e_1_3_2_63_2
e_1_3_2_23_2
e_1_3_2_44_2
e_1_3_2_25_2
e_1_3_2_46_2
e_1_3_2_67_2
e_1_3_2_61_2
e_1_3_2_15_2
e_1_3_2_38_2
e_1_3_2_8_2
e_1_3_2_17_2
e_1_3_2_59_2
e_1_3_2_6_2
e_1_3_2_19_2
e_1_3_2_30_2
e_1_3_2_53_2
e_1_3_2_32_2
e_1_3_2_51_2
e_1_3_2_11_2
e_1_3_2_34_2
e_1_3_2_57_2
e_1_3_2_4_2
e_1_3_2_13_2
e_1_3_2_36_2
e_1_3_2_55_2
e_1_3_2_2_2
References_xml – ident: e_1_3_2_28_2
  doi: 10.7717/peerj.798
– ident: e_1_3_2_57_2
  doi: 10.3389/fimmu.2017.00959
– ident: e_1_3_2_4_2
  doi: 10.3201/eid1701.091101p1
– ident: e_1_3_2_10_2
  doi: 10.1093/infdis/jix045
– ident: e_1_3_2_58_2
  doi: 10.4049/jimmunol.1700384
– ident: e_1_3_2_60_2
  doi: 10.1091/mbc.e06-04-0318
– ident: e_1_3_2_22_2
  doi: 10.1128/mBio.00668-17
– ident: e_1_3_2_35_2
  doi: 10.1096/fj.11-196915
– ident: e_1_3_2_32_2
  doi: 10.1074/jbc.M412882200
– ident: e_1_3_2_43_2
  doi: 10.1038/sj.cdd.4401833
– ident: e_1_3_2_29_2
  doi: 10.1002/wrna.1162
– ident: e_1_3_2_48_2
  doi: 10.1038/ni1584
– ident: e_1_3_2_39_2
  doi: 10.1007/978-3-662-09889-9_3
– ident: e_1_3_2_20_2
  doi: 10.1128/JVI.00600-09
– ident: e_1_3_2_41_2
  doi: 10.1096/fj.10-168799
– ident: e_1_3_2_53_2
  doi: 10.1093/emboj/cdg251
– ident: e_1_3_2_56_2
  doi: 10.2741/2692
– ident: e_1_3_2_9_2
  doi: 10.1586/erv.12.78
– ident: e_1_3_2_13_2
  doi: 10.1126/science.1257147
– ident: e_1_3_2_7_2
  doi: 10.1093/infdis/170.1.34
– ident: e_1_3_2_30_2
  doi: 10.1083/jcb.147.7.1431
– ident: e_1_3_2_63_2
  doi: 10.1128/JVI.02220-10
– ident: e_1_3_2_34_2
  doi: 10.1128/JVI.78.16.8455-8467.2004
– ident: e_1_3_2_66_2
  doi: 10.1016/S0021-9258(18)33352-0
– ident: e_1_3_2_11_2
  doi: 10.1371/journal.pmed.1001807
– ident: e_1_3_2_15_2
  doi: 10.1371/journal.pbio.0020432
– ident: e_1_3_2_65_2
  doi: 10.1128/jvi.54.2.643-645.1985
– ident: e_1_3_2_40_2
  doi: 10.1091/mbc.e05-02-0124
– ident: e_1_3_2_38_2
  doi: 10.1073/pnas.0703348104
– ident: e_1_3_2_25_2
  doi: 10.1074/jbc.M709563200
– ident: e_1_3_2_47_2
  doi: 10.1016/j.tcb.2015.02.001
– ident: e_1_3_2_59_2
  doi: 10.1371/journal.ppat.1000108
– ident: e_1_3_2_16_2
  doi: 10.1126/science.1077905
– ident: e_1_3_2_18_2
  doi: 10.1186/1743-422X-3-33
– ident: e_1_3_2_33_2
  doi: 10.1091/mbc.01-05-0221
– ident: e_1_3_2_42_2
  doi: 10.1016/S1074-7613(00)00014-5
– ident: e_1_3_2_21_2
  doi: 10.1128/JVI.05784-11
– ident: e_1_3_2_2_2
  doi: 10.3201/eid1908.130465
– ident: e_1_3_2_12_2
  doi: 10.1086/657087
– ident: e_1_3_2_31_2
  doi: 10.1016/0003-9861(87)90622-9
– ident: e_1_3_2_54_2
  doi: 10.1186/1743-422X-3-33
– ident: e_1_3_2_55_2
  doi: 10.1074/jbc.M114.550657
– ident: e_1_3_2_36_2
  doi: 10.1016/j.chom.2007.08.006
– ident: e_1_3_2_46_2
  doi: 10.1074/mcp.M116.062448
– ident: e_1_3_2_17_2
  doi: 10.1371/journal.ppat.1002413
– ident: e_1_3_2_62_2
  doi: 10.1038/nrm1618
– ident: e_1_3_2_6_2
  doi: 10.1086/341408
– ident: e_1_3_2_24_2
  doi: 10.1128/JVI.02138-16
– ident: e_1_3_2_68_2
  doi: 10.1128/jvi.61.8.2480-2488.1987
– ident: e_1_3_2_5_2
  doi: 10.1093/infdis/119.6.668
– ident: e_1_3_2_64_2
  doi: 10.1128/JVI.00260-10
– ident: e_1_3_2_52_2
  doi: 10.3389/fmicb.2012.00092
– ident: e_1_3_2_26_2
  doi: 10.1099/vir.0.005629-0
– ident: e_1_3_2_3_2
  doi: 10.1093/cid/ciq163
– ident: e_1_3_2_14_2
  doi: 10.1126/science.aaf5211
– ident: e_1_3_2_50_2
  doi: 10.1016/j.virol.2012.11.017
– ident: e_1_3_2_67_2
  doi: 10.1128/jvi.62.11.4216-4223.1988
– ident: e_1_3_2_19_2
  doi: 10.1038/sj.embor.7400510
– ident: e_1_3_2_23_2
  doi: 10.1016/j.virol.2010.06.047
– ident: e_1_3_2_37_2
  doi: 10.1128/JVI.78.16.8582-8592.2004
– ident: e_1_3_2_44_2
  doi: 10.1016/j.neulet.2006.09.074
– ident: e_1_3_2_8_2
  doi: 10.1056/NEJMoa1101245
– ident: e_1_3_2_51_2
  doi: 10.1126/science.aaf1220
– ident: e_1_3_2_61_2
  doi: 10.1083/jcb.200512082
– ident: e_1_3_2_45_2
  doi: 10.7554/eLife.00498
– ident: e_1_3_2_49_2
  doi: 10.1128/JVI.00647-16
– ident: e_1_3_2_27_2
  doi: 10.1371/journal.pone.0038723
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Snippet The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore cellular...
Viruses hijack host machinery and regulate cellular homeostasis to actively replicate their genome, propagate, and cause disease. In retaliation, cells possess...
ABSTRACT The integrated stress response (ISR) is a cellular response system activated upon different types of stresses, including viral infection, to restore...
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Aggregation Database
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SubjectTerms Animals
Caliciviridae Infections - immunology
Cytoplasmic Granules - immunology
Cytoplasmic Granules - virology
DNA Helicases - immunology
Editor's Pick
eIF-2 Kinase - immunology
eIF2α
Eukaryotic Initiation Factor-2 - immunology
Host-Microbe Biology
Host-Pathogen Interactions
Immune Evasion
Immunity, Innate
integrated stress response
Mice
mouse norovirus
Phosphorylation
Poly-ADP-Ribose Binding Proteins - immunology
Protein Biosynthesis
protein kinase R
protein translation
RNA Helicases - immunology
RNA Recognition Motif Proteins - immunology
stress granules
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Replication
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Title Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis
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