SH3 Domain-Mediated Recruitment of Host Cell Amphiphysins by Alphavirus nsP3 Promotes Viral RNA Replication

English version České info

Among the four non-structural proteins of alphaviruses the function of nsP3 is the least well understood. NsP3 is a component of the viral replication complex, and composed of a conserved aminoterminal macro domain implicated in viral RNA synthesis, and a poorly conserved carboxyterminal region. Despite the lack of overall homology we noted a carboxyterminal proline-rich sequence motif shared by many alphaviral nsP3 proteins, and found it to serve as a preferred target site for the Src-homology 3 (SH3) domains of amphiphysin-1 and -2. Nsp3 proteins of Semliki Forest (SFV), Sindbis (SINV), and Chikungunya viruses all showed avid and SH3-dependent binding to amphiphysins. Upon alphavirus infection the intracellular distribution of amphiphysin was dramatically altered and colocalized with nsP3. Mutations in nsP3 disrupting the amphiphysin SH3 binding motif as well as RNAi-mediated silencing of amphiphysin-2 expression resulted in impaired viral RNA replication in HeLa cells infected with SINV or SFV. Infection of Balb/c mice with SFV carrying an SH3 binding-defective nsP3 was associated with significantly decreased mortality. These data establish SH3 domain-mediated binding of nsP3 with amphiphysin as an important host cell interaction promoting alphavirus replication.

Vyšlo v časopise: SH3 Domain-Mediated Recruitment of Host Cell Amphiphysins by Alphavirus nsP3 Promotes Viral RNA Replication. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002383
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002383

Souhrn

Zdroje

1. GriffinDE 2007 Alphaviruses. Field's Virology. 5th edition Philadelphia Lippincott, Williams & Wilkins 1023 1068

2. StraussJHStraussEG 1994 The alphaviruses: gene expression, replication, and evolution. Microbiol Rev 58 491 562

3. SchwartzOAlbertML 2010 Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol 8 491 500

4. SpuulPBalistreriGKääriäinenLAholaT 2010 Phosphatidylinositol 3-kinase-, actin-, and microtubule-dependent transport of Semliki Forest Virus replication complexes from the plasma membrane to modified lysosomes. J Virol 84 7543 7557

5. KujalaPIkäheimonenAEhsaniNVihinenHAuvinenP 2001 Biogenesis of the Semliki Forest virus RNA replication complex. J Virol 75 3873 3884

6. KääriäinenLAholaT 2002 Functions of alphavirus nonstructural proteins in RNA replication. Prog Nucleic Acid Res Mol Biol 71 187 222

7. DeIFata-HartleyCSawickiSGSawickiDL 2003 Functional analysis of nsP3 phosphoprotein mutants of Sindbis virus. J Virol 77 13106 13116

8. MaletHCoutardBJamalSDutartreHPapageorgiouN 2009 The crystal structures of Chikungunya and Venezuelan equine encephalitis virus nsP3 macro domains define a conserved adenosine binding pocket. J Virol 83 6534 6545

9. NeuvonenMAholaT 2009 Differential activities of cellular and viral macro domain proteins in binding of ADP-ribose metabolites. J Mol Biol 385 212 225

10. ParkEGriffinDE 2009 The nsP3 macro domain is important for Sindbis virus replication in neurons and neurovirulence in mice. Virology 388 305 314

11. TuittilaMHinkkanenAE 2003 Amino acid mutations in the replicase protein nsP3 of Semliki Forest virus cumulatively affect neurovirulence. J Gen Virol 84 1525 1533

12. VihinenHAholaTTuittilaMMeritsAKääriäinenL 2001 Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3. J Biol Chem 276 5745 5752

13. CristeaIMCarrollJWRoutMPRiceCMChaitBT 2006 Tracking and elucidating alphavirus-host protein interactions. J Biol Chem 281 30269 30278

14. GorchakovRGarmashovaNFrolovaEFrolovI 2008 Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol 82 10088 10101

15. SalonenAVasiljevaLMeritsAMagdenJJokitaloE 2003 Properly folded nonstructural polyprotein directs the semliki forest virus replication complex to the endosomal compartment. J Virol 77 1691 1702

16. KanekoTLiLLiSS 2008 The SH3 domain--a family of versatile peptide- and protein-recognition module. Front Biosci 13 4938 4952

17. MayerBJ 2001 SH3 domains: complexity in moderation. J Cell Sci 114 1253 1263

18. SakselaKChengGBaltimoreD 1995 Proline-rich (PxxP) motifs in HIV-1 Nef bind to SH3 domains of a subset of Src kinases and are required for the enhanced growth of Nef+ viruses but not for down-regulation of CD4. EMBO J 14 484 491

19. KärkkäinenSHiipakkaMWangJHKleinoIVähä-JaakkolaM 2006 Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome. EMBO Rep 7 186 191

20. HeikkinenLSKazlauskasAMelenKWagnerRZieglerT 2008 Avian and 1918 Spanish influenza a virus NS1 proteins bind to Crk/CrkL Src homology 3 domains to activate host cell signaling. J Biol Chem 283 5719 5727

21. KestiTRuppeltAWangJHLissMWagnerR 2007 Reciprocal regulation of SH3 and SH2 domain binding via tyrosine phosphorylation of a common site in CD3epsilon. J Immunol 179 878 885

22. PietrekMBrinkmannMMGlowackaIEnlundAHavemeierA 2010 Role of the Kaposi's sarcoma-associated herpesvirus K15 SH3 binding site in inflammatory signaling and B-cell activation. J Virol 84 8231 8240

23. SchmaierAAZouZKazlauskasAEmert-SedlakLFongKP 2009 Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role. Proc Natl Acad Sci U S A 106 21167 21172

24. ThompsonOMooreCJHussainSAKleinoIPeckhamM 2010 Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan. J Cell Sci 123 118 127

25. VingadassalomDKazlauskasASkehanBChengHCMagounL 2009 Insulin receptor tyrosine kinase substrate links the E. coli O157:H7 actin assembly effectors Tir and EspF(U) during pedestal formation. Proc Natl Acad Sci U S A 106 6754 6759

26. DawsonJCLeggJAMacheskyLM 2006 Bar domain proteins: a role in tubulation, scission and actin assembly in clathrin-mediated endocytosis. Trends Cell Biol 16 493 498

27. PrendergastGCMullerAJRamalingamAChangMY 2009 BAR the door: cancer suppression by amphiphysin-like genes. Biochim Biophys Acta 1795 25 36

28. FrolovaEGorchakovRGarmashovaNAtashevaSVergaraLA 2006 Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol 80 4122 4134

29. WiggePMcMahonHT 1998 The amphiphysin family of proteins and their role in endocytosis at the synapse. Trends Neurosci 21 339 344

30. ZhangBZelhofAC 2002 Amphiphysins: raising the BAR for synaptic vesicle recycling and membrane dynamics. Bin-Amphiphysin-Rvsp. Traffic 3 452 460

31. RazzaqASuYMehrenJEMizuguchiKJacksonAP 2000 Characterisation of the gene for Drosophila amphiphysin. Gene 241 167 174

32. LarsonSMDavidsonAR 2000 The identification of conserved interactions within the SH3 domain by alignment of sequences and structures. Protein Sci 9 2170 2180

33. GrahamTRKozlovMM 2010 Interplay of proteins and lipids in generating membrane curvature. Curr Opin Cell Biol 22 430 436

34. HabermannB 2004 The BAR-domain family of proteins: a case of bending and binding? EMBO Rep 5 250 255

35. FroshauerSKartenbeckJHeleniusA 1988 Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes. J Cell Biol 107 2075 2086

36. GrabsDSlepnevVISongyangZDavidCLynchM 1997 The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding consensus sequence. J Biol Chem 272 13419 13425

37. OwenDJWiggePVallisYMooreJDEvansPR 1998 Crystal structure of the amphiphysin-2 SH3 domain and its role in the prevention of dynamin ring formation. EMBO J 17 5273 5285

38. Pineda-LucenaAHoCSMaoDYShengYLaisterRC 2005 A structure-based model of the c-Myc/Bin1 protein interaction shows alternative splicing of Bin1 and c-Myc phosphorylation are key binding determinants. J Mol Biol 351 182 194

39. GalbraithSESheahanBJAtkinsGJ 2006 Deletions in the hypervariable domain of the nsP3 gene attenuate Semliki Forest virus virulence. J Gen Virol 87 937 947

40. LastarzaMWGrakouiARiceCM 1994 Deletion and duplication mutations in the C-terminal nonconserved region of Sindbis virus nsP3: effects on phosphorylation and on virus replication in vertebrate and invertebrate cells. Virology 202 224 232

41. MasumiAAizakiHSuzukiTDuHadawayJBPrendergastGC 2005 Reduction of hepatitis C virus NS5A phosphorylation through its interaction with amphiphysin II. Biochem Biophys Res Commun 336 572 578

42. ZechBKurtenbachAKriegerNStrandDBlenckeS 2003 Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein. J Gen Virol 84 555 560

43. FerrarisPBlanchardERoingeardP 2010 Ultrastructural and biochemical analyses of hepatitis C virus-associated host cell membranes. J Gen Virol 91 2230 2237

44. MoradpourDGosertREggerDPeninFBlumHE 2003 Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex. Antiviral Res 60 103 109

45. TuittilaMTSantagatiMGRöyttäMMäättäJAHinkkanenAE 2000 Replicase complex genes of Semliki Forest virus confer lethal neurovirulence. J Virol 74 4579 4589

46. RiceCMLevisRStraussJHHuangHV 1987 Production of infectious RNA transcripts from Sindbis virus cDNA clones: mapping of lethal mutations, rescue of a temperature-sensitive marker, and in vitro mutagenesis to generate defined mutants. J Virol 61 3809 3819

47. SpuulPSalonenAMeritsAJokitaloEKääriäinenL 2007 Role of the amphipathic peptide of Semliki forest virus replicase protein nsP1 in membrane association and virus replication. J Virol 81 872 883

48. PohjalaLBaraiVAzhayevALapinjokiSAholaT 2008 A luciferase-based screening method for inhibitors of alphavirus replication applied to nucleoside analogues. Antiviral Res 78 215 222

49. KeränenSKääriäinenL 1974 Isolation and basic characterization of temperature-sensitive mutants from Semliki Forest virus. Acta Pathol Microbiol Scand B Microbiol Immunol 82 810 820