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The DEAD-box RNA Helicase DDX6 is Required for Efficient Encapsidation of a Retroviral Genome
Viruses have to encapsidate their own genomes during the assembly process. For most RNA viruses, there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation. However, the roles of host proteins in this process are not understood. Here we find that the cellular DEAD-box RNA helicase DDX6 is required for efficient genome packaging of foamy virus, a spumaretrovirus. After infection, a significant amount of DDX6, normally concentrated in P bodies and stress granules, re-localizes to the pericentriolar site where viral RNAs and Gag capsid proteins are concentrated and capsids are assembled. Knockdown of DDX6 by siRNA leads to a decreased level of viral nucleic acids in extracellular particles, although viral protein expression, capsid assembly and release, and accumulation of viral RNA and Gag protein at the assembly site are little affected. DDX6 does not interact stably with Gag proteins nor is it incorporated into particles. However, we find that the ATPase/helicase motif of DDX6 is essential for viral replication. This suggests that the ATP hydrolysis and/or the RNA unwinding activities of DDX6 function in moderating the viral RNA conformation and/or viral RNA-Gag ribonucleoprotein complex in a transient manner to facilitate incorporation of the viral RNA into particles. These results reveal a unique role for a highly conserved cellular protein of RNA metabolism in specifically re-locating to the site of viral assembly for its function as a catalyst in retroviral RNA packaging.
Vyšlo v časopise: The DEAD-box RNA Helicase DDX6 is Required for Efficient Encapsidation of a Retroviral Genome. PLoS Pathog 7(10): e32767. doi:10.1371/journal.ppat.1002303
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002303Souhrn
Viruses have to encapsidate their own genomes during the assembly process. For most RNA viruses, there are sequences within the viral RNA and virion proteins needed for high efficiency of genome encapsidation. However, the roles of host proteins in this process are not understood. Here we find that the cellular DEAD-box RNA helicase DDX6 is required for efficient genome packaging of foamy virus, a spumaretrovirus. After infection, a significant amount of DDX6, normally concentrated in P bodies and stress granules, re-localizes to the pericentriolar site where viral RNAs and Gag capsid proteins are concentrated and capsids are assembled. Knockdown of DDX6 by siRNA leads to a decreased level of viral nucleic acids in extracellular particles, although viral protein expression, capsid assembly and release, and accumulation of viral RNA and Gag protein at the assembly site are little affected. DDX6 does not interact stably with Gag proteins nor is it incorporated into particles. However, we find that the ATPase/helicase motif of DDX6 is essential for viral replication. This suggests that the ATP hydrolysis and/or the RNA unwinding activities of DDX6 function in moderating the viral RNA conformation and/or viral RNA-Gag ribonucleoprotein complex in a transient manner to facilitate incorporation of the viral RNA into particles. These results reveal a unique role for a highly conserved cellular protein of RNA metabolism in specifically re-locating to the site of viral assembly for its function as a catalyst in retroviral RNA packaging.
Zdroje
1. SwitzerWMBhullarVShanmugamVCongMEParekhB 2004 Frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates. J Virol 78 2780 2789
2. FischerNHeinkeleinMLindemannDEnssleJBaumC 1998 Foamy virus particle formation. J Virol 72 1610 1615
3. SfakianosJNLaCasseRAHunterE 2003 The M-PMV cytoplasmic targeting-retention signal directs nascent Gag polypeptides to a pericentriolar region of the cell. Traffic 4 660 670
4. YuSFEastmanSWLinialML 2006 Foamy virus capsid assembly occurs at a pericentriolar region through a cytoplasmic targeting/retention signal in Gag. Traffic 7 966 977
5. PooleEStrappePMokHPHicksRLeverAM 2005 HIV-1 Gag-RNA interaction occurs at a perinuclear/centrosomal site; analysis by confocal microscopy and FRET. Traffic 6 741 745
6. AndersonPKedershaN 2006 RNA granules. J Cell Biol 172 803 808
7. AndersonPKedershaN 2008 Stress granules: the Tao of RNA triage. Trends Biochem Sci 33 141 150
8. BeckhamCJParkerR 2008 P bodies, stress granules, and viral life cycles. Cell Host Microbe 3 206 212
9. FurtakVMulkyARawlingsSAKozhayaLLeeK 2010 Perturbation of the P-body component Mov10 inhibits HIV-1 infectivity. PLoS ONE 5 e9081
10. WangXHanYDangYFuWZhouT 2010 Moloney leukemia virus 10 (MOV10) protein inhibits retrovirus replication. J Biol Chem 285 14346 14355
11. BurdickRSmithJLChaipanCFriewYChenJ 2010 P body-associated protein Mov10 inhibits HIV-1 replication at multiple stages. J Virol 84 10241 10253
12. AyeMIrwinBBeliakova-BethellNChenEGarrusJ 2004 Host factors that affect Ty3 retrotransposition in Saccharomyces cerevisiae. Genetics 168 1159 1176
13. Beliakova-BethellNBeckhamCGiddingsTWineyMParkerR 2006 Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components. RNA 12 94 101
14. DutkoJAKennyAEGamacheERCurcioMJ 2010 5′ to 3′ mRNA decay factors colocalize with Ty1 Gag and human APOBEC3G and promote Ty1 retrotransposition. J Virol 84 5052 5066
15. CheckleyMANagashimaKLockettSJNyswanerKMGarfinkelDJ 2010 P-body components are required for Ty1 retrotransposition during assembly of retrotransposition-competent virus-like particles. Mol Cell Biol 30 382 398
16. WestonASommervilleJ 2006 Xp54 and related (DDX6-like) RNA helicases: roles in messenger RNP assembly, translation regulation and RNA degradation. Nucleic Acids Res 34 3082 3094
17. CordinOBanroquesJTannerNKLinderP 2006 The DEAD-box protein family of RNA helicases. Gene 367 17 37
18. SchellerNMinaLBGalaoRPChariAGimenez-BarconsM 2009 Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates. Proc Natl Acad Sci U S A 106 13517 13522
19. JangraRKYiMLemonSM 2010 DDX6 (Rck/p54) is required for efficient hepatitis C virus replication but not for internal ribosome entry site-directed translation. J Virol 84 6810 6824
20. AriumiYKurokiMKiAbeDansakoHIkedaM 2007 DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol 81 13922 13926
21. Chable-BessiaCMezianeOLatreilleDTribouletRZamborliniA 2009 Suppression of HIV-1 replication by microRNA effectors. Retrovirology 6 26
22. NathansRChuCYSerquinaAKLuCCCaoH 2009 Cellular microRNA and P bodies modulate host-HIV-1 interactions. Mol Cell 34 696 709
23. YedavalliVSRKNeuveutCYhChiKleimanLJeangKT 2004 Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell 119 381 392
24. LinialML 1999 Foamy viruses are unconventional retroviruses. J Virol 73 1747 1755
25. YuSFLinialML 1993 Analysis of the role of the bel and bet open reading frames of human foamy virus by using a new quantitative assay. J Virol 67 6618 6624
26. TilsnerJLinnikOChristensenNMBellKRobertsIM 2009 Live-cell imaging of viral RNA genomes using a Pumilio-based reporter. Plant J 57 758 770
27. LeeEGLinialML 2008 The C terminus of foamy retrovirus Gag contains determinants for encapsidation of Pol protein into virions. J Virol 82 10803 10810
28. HeinkeleinMLeursCRammlingMPetersKHanenbergH 2002 Pregenomic RNA is required for efficient incorporation of Pol polyprotein into foamy virus capsids. J Virol 76 10069 10073
29. CollerJMTuckerMShethUValencia-SanchezMAParkerR 2001 The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA 7 1717 1727
30. Fenger-GronMFillmanCNorrildBLykke-AndersenJ 2005 Multiple processing body factors and the ARE binding protein TTP activate mRNA decapping. Mol Cell 20 905 915
31. CollerJParkerR 2005 General translational repression by activators of mRNA decapping. Cell 122 875 886
32. ChuCYRanaTM 2006 Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54. PLoS Biol 4 e210
33. NissanTRajyaguruPSheMSongHParkerR 2010 Decapping activators in Saccharomyces cerevisiae act by multiple mechanisms. Mol Cell 39 773 783
34. HashimotoKNakagawaYMorikawaHNikiMEgashiraY 2001 Co-overexpression of DEAD box protein rck/p54 and c-myc protein in human colorectal adenomas and the relevance of their expression in cultured cell lines. Carcinogenesis 22 1965 1970
35. AkaoYMatsumotoKOhguchiKNakagawaYYoshidaH 2006 Human DEAD-box/RNA unwindase rck/p54 contributes to maintenance of cell growth by affecting cell cycle in cultured cells. Int J Oncol 29 41 48
36. MatsuiTHogetsuKUsukuraJSatoTKumasakaT 2006 Structural insight of human DEAD-box protein rck/p54 into its substrate recognition with conformational changes. Genes Cells 11 439 452
37. KahvejianASvitkinYVSukariehRM'BoutchouMNISonenbergN 2005 Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor which acts via multiple mechanisms. Genes Dev 19 104 113
38. MeieringCDRubioCMayCLinialML 2001 Cell-type-specific regulation of the two foamy virus promoters. J Virol 75 6547 6557
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