| Structural highlights
Function
POLG_WNV Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (By similarity).[1] [2] [3] [4] [5] prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated (By similarity).[6] [7] [8] [9] [10] Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).[11] [12] [13] [14] [15] Non-structural protein 1 is involved in virus replication and regulation of the innate immune response (By similarity).[16] [17] [18] [19] [20] Non-structural protein 2A may be involved viral RNA replication and capsid assembly (Potential).[21] [22] [23] [24] [25] Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).[26] [27] [28] [29] [30] Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction (By similarity).[31] [32] [33] [34] [35] Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase (By similarity).[36] [37] [38] [39] [40] Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter (By similarity).[41] [42] [43] [44] [45] Non-structural protein 4B inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (By similarity).[46] [47] [48] [49] [50] RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host JAK1 and TYK2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).[51] [52] [53] [54] [55]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The two-component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication. Here, we report the crystal structure of WNV NS2B-NS3pro both in a substrate-free form and in complex with the trypsin inhibitor aprotinin/BPTI. We show that aprotinin binds in a substrate-mimetic fashion in which the productive conformation of the protease is fully formed, providing evidence for an "induced fit" mechanism of catalysis and allowing us to rationalize the distinct substrate specificities of WNV and DV proteases. We also show that the NS2B cofactor of WNV can adopt two very distinct conformations and that this is likely to be a general feature of flaviviral proteases, providing further opportunities for regulation. Finally, by comparing the flaviviral proteases with the more distantly related Hepatitis C virus, we provide insights into the evolution of the Flaviviridae fold. Our work should expedite the design of protease inhibitors to treat a range of flaviviral infections.
Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold.,Aleshin AE, Shiryaev SA, Strongin AY, Liddington RC Protein Sci. 2007 May;16(5):795-806. Epub 2007 Mar 30. PMID:17400917[56]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Chu JJ, Ng ML. Infectious entry of West Nile virus occurs through a clathrin-mediated endocytic pathway. J Virol. 2004 Oct;78(19):10543-55. PMID:15367621 doi:10.1128/JVI.78.19.10543-10555.2004
- ↑ Munoz-Jordan JL, Laurent-Rolle M, Ashour J, Martinez-Sobrido L, Ashok M, Lipkin WI, Garcia-Sastre A. Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses. J Virol. 2005 Jul;79(13):8004-13. PMID:15956546 doi:10.1128/JVI.79.13.8004-8013.2005
- ↑ Zhou Y, Ray D, Zhao Y, Dong H, Ren S, Li Z, Guo Y, Bernard KA, Shi PY, Li H. Structure and function of flavivirus NS5 methyltransferase. J Virol. 2007 Apr;81(8):3891-903. Epub 2007 Jan 31. PMID:17267492 doi:10.1128/JVI.02704-06
- ↑ Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol. 2010 Apr;84(7):3503-15. doi: 10.1128/JVI.01161-09. Epub 2010 Jan 27. PMID:20106931 doi:10.1128/JVI.01161-09
- ↑ Issur M, Geiss BJ, Bougie I, Picard-Jean F, Despins S, Mayette J, Hobdey SE, Bisaillon M. The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure. RNA. 2009 Dec;15(12):2340-50. doi: 10.1261/rna.1609709. Epub 2009 Oct 22. PMID:19850911 doi:10.1261/rna.1609709
- ↑ Aleshin AE, Shiryaev SA, Strongin AY, Liddington RC. Structural evidence for regulation and specificity of flaviviral proteases and evolution of the Flaviviridae fold. Protein Sci. 2007 May;16(5):795-806. Epub 2007 Mar 30. PMID:17400917 doi:10.1110/ps.072753207
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