Genetic interactions among the West Nile virus methyltransferase, the RNA-dependent RNA polymerase, and the 5' stem-loop of genomic RNA.
| References: | J Virol. 2005 Jun;79(11):6631-43. (PMID: 15890901) Virology. 2008 Mar 30;373(1):1-13. (PMID: 18258275) Virology. 2002 Jul 20;299(1):122-32. (PMID: 12167347) J Virol. 2003 Oct;77(19):10623-9. (PMID: 12970446) J Virol. 1999 Apr;73(4):3108-16. (PMID: 10074162) Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12898-903. (PMID: 9371772) Antimicrob Agents Chemother. 2005 Dec;49(12):4980-8. (PMID: 16304161) J Biol Chem. 2005 Feb 11;280(6):4429-35. (PMID: 15574411) Virology. 1993 Nov;197(1):265-73. (PMID: 8212562) J Virol. 2007 Apr;81(8):3891-903. (PMID: 17267492) J Clin Microbiol. 2001 Apr;39(4):1264-71. (PMID: 11283039) Genes Dev. 1997 Dec 15;11(24):3319-26. (PMID: 9407025) J Virol. 2008 May;82(9):4295-307. (PMID: 18305027) J Virol Methods. 2001 Mar;92(1):37-44. (PMID: 11164916) J Virol. 2004 Aug;78(15):8159-71. (PMID: 15254187) Virology. 2008 Jul 20;377(1):1-6. (PMID: 18501946) J Virol. 2006 Sep;80(17):8362-70. (PMID: 16912287) Virology. 1981 Sep;113(2):544-55. (PMID: 7269253) J Biol Chem. 1999 Nov 19;274(47):33714-22. (PMID: 10559263) J Biol Chem. 2007 Apr 6;282(14):10678-89. (PMID: 17287213) J Biol Chem. 2001 Oct 26;276(43):39926-37. (PMID: 11546770) Mol Cell. 2004 Jan 16;13(1):77-89. (PMID: 14731396) Genes Dev. 1997 Dec 15;11(24):3306-18. (PMID: 9407024) Protein Sci. 2007 Jun;16(6):1133-45. (PMID: 17473012) Virology. 1991 Oct;184(2):707-15. (PMID: 1716026) Genes Dev. 2006 Aug 15;20(16):2238-49. (PMID: 16882970) Virology. 2005 Jan 20;331(2):375-86. (PMID: 15629780) Adv Virus Res. 2000;55:135-84. (PMID: 11050942) Virology. 1985 Jan 15;140(1):68-79. (PMID: 2578239) J Virol. 1993 Feb;67(2):989-96. (PMID: 8380474) Virology. 1979 Jul 15;96(1):159-65. (PMID: 111410) J Virol. 2003 Sep;77(18):10004-14. (PMID: 12941911) J Biol Chem. 2002 Nov 1;277(44):41978-86. (PMID: 12181314) J Gen Virol. 2007 Aug;88(Pt 8):2228-2236. (PMID: 17622627) EMBO J. 2002 Jun 3;21(11):2757-68. (PMID: 12032088) J Virol. 2007 May;81(9):4412-21. (PMID: 17301144) J Virol. 2001 Jul;75(14):6719-28. (PMID: 11413342) Virology. 1996 Feb 15;216(2):317-25. (PMID: 8607261) J Virol. 1998 Sep;72(9):7510-22. (PMID: 9696848) J Virol. 1999 Jun;73(6):4611-21. (PMID: 10233920) J Virol. 1993 Apr;67(4):2034-42. (PMID: 8383225) Mol Cell. 2007 Jan 12;25(1):85-97. (PMID: 17218273) Adv Virus Res. 2003;59:177-228. (PMID: 14696330) J Virol. 2002 Jun;76(12):5847-56. (PMID: 12021317) |
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| Grant Information: | U54-AI057158 United States AI NIAID NIH HHS; U01 AI061193 United States AI NIAID NIH HHS; N01AI25490 United States AI NIAID NIH HHS; U54 AI057158 United States AI NIAID NIH HHS; N0I-AI-25490 United States AI NIAID NIH HHS |
| Substance Nomenclature: | 0 (RNA, Viral) 0 (Viral Proteins) EC 2.1.1.- (Methyltransferases) EC 2.7.7.48 (RNA-Dependent RNA Polymerase) |
| Entry Date(s): | Date Created: 20080502 Date Completed: 20080715 Latest Revision: 20211020 |
| Update Code: | 20221213 |
| PubMed Central ID: | PMC2446981 |
| DOI: | 10.1128/JVI.00654-08 |
| PMID: | 18448528 |
| Autor: | Zhang B; Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA., Dong H, Zhou Y, Shi PY |
| Jazyk: | angličtina |
| Zdroj: | Journal of virology [J Virol] 2008 Jul; Vol. 82 (14), pp. 7047-58. Date of Electronic Publication: 2008 Apr 30. |
| DOI: | 10.1128/JVI.00654-08 |
| Abstrakt: | Flavivirus methyltransferase catalyzes both guanine N7 and ribose 2'-OH methylations of the viral RNA cap (GpppA-RNA-->m(7)GpppAm-RNA). The methyltransferase is physically linked to an RNA-dependent RNA polymerase (RdRp) in the flaviviral NS5 protein. Here, we report genetic interactions of West Nile virus (WNV) methyltransferase with the RdRp and the 5'-terminal stem-loop of viral genomic RNA. Genome-length RNAs, containing amino acid substitutions of D146 (a residue essential for both cap methylations) in the methyltransferase, were transfected into BHK-21 cells. Among the four mutant RNAs (D146L, D146P, D146R, and D146S), only D146S RNA generated viruses in transfected cells. Sequencing of the recovered viruses revealed that, besides the D146S change in the methyltransferase, two classes of compensatory mutations had reproducibly emerged. Class 1 mutations were located in the 5'-terminal stem-loop of the genomic RNA (a G35U substitution or U38 insertion). Class 2 mutations resided in NS5 (K61Q in methyltransferase and W751R in RdRp). Mutagenesis analysis, using a genome-length RNA and a replicon of WNV, demonstrated that the D146S substitution alone was lethal for viral replication; however, the compensatory mutations rescued replication, with the highest rescuing efficiency occurring when both classes of mutations were present. Biochemical analysis showed that a low level of N7 methylation of the D146S methyltransferase is essential for the recovery of adaptive viruses. The methyltransferase K61Q mutation facilitates viral replication through improved N7 methylation activity. The RdRp W751R mutation improves viral replication through an enhanced polymerase activity. Our results have clearly established genetic interactions among flaviviral methyltransferase, RdRp, and the 5' stem-loop of the genomic RNA. |
| Databáze: | MEDLINE |
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