title: Mechanism of preferential packaging of negative sense genomic RNA by viral nucleoproteins in Crimean-Congo hemorrhagic Fever virus.
abstract: The Crimean-Congo Hemorrhagic Fever (CCHF) is an infectious disease of high virulence and mortality caused by a negative sense RNA nairovirus. The genomic RNA of CCHFV is enwrapped by its nucleoprotein. Positively charged residues on CCHFV nucleoprotein provide multiple binding sites to facilitate genomic RNA encapsidation. In the present work, we investigated the mechanism underlying preferential packaging of the negative sense genomic RNA by CCHFV nucleoprotein in the presence of host cell RNAs during viral assembly. The work included genome sequence analyses for different families of negative and positive sense RNA viruses, using serial docking experiments and molecular dynamic simulations. Our results indicated that the main determinant parameter of the nucleoprotein binding affinity for negative sense RNA is the ratio of purine/pyrimidine in the RNA molecule. A negative sense RNA with a purine/pyrimidine ratio (>1) higher than that of a positive sense RNA (<1) exhibits higher affinity for the nucleoprotein. Our calculations revealed that a negative sense RNA expresses about 0.5 kJ/mol higher binding energy per nucleotide compared to a positive sense RNA. This energy difference produces a binding energy high enough to make the negative sense RNA, the preferred substrate for packaging by CCHFV nucleoprotein in the presence of cellular or complementary positive sense RNAs. The outcome of this study may contribute to ongoing researches on other viral diseases caused by negative sense RNA viruses such as Ebola virus which poses a security threat to all humanity.
authors: Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran, mrdayer@scu.ac.ir.
authors: Mohammad Reza
authors: MR
authors: Dayer
authors: Mohammad Saaid
authors: MS
authors: Dayer
authors: Seyedeh Elham
authors: SE
authors: Rezatofighi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D016679:Genome, Viral; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000737:chemistry* / Q000235:genetics; D054884:Host-Pathogen Interactions; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000737:chemistry* / Q000235:genetics; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D019065:Virus Assembly
chemical_list: D009698:Nucleoproteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins
references: Biochemistry. 2008 Feb 19;47(7):2099-109
references: 18197707
references: Structure. 2003 Oct;11(10):1219-26
references: 14527390
references: J Biomed Sci. 2013 Sep 12;20:67
references: 24024748
references: Arch Biochem Biophys. 1996 Mar 1;327(1):189-99
references: 8615690
references: Virol J. 2008 Jan 15;5:7
references: 18197964
references: Cell. 1985 May;41(1):259-67
references: 2986844
references: RNA. 2000 Feb;6(2):270-81
references: 10688365
references: Lancet Infect Dis. 2006 Apr;6(4):203-14
references: 16554245
references: PLoS Pathog. 2013 Mar;9(3):e1003275
references: 23555270
references: J Virol. 2000 Nov;74(21):9946-52
references: 11024122
references: Antiviral Res. 2004 Dec;64(3):145-60
references: 15550268
references: J Virol. 2006 Sep;80(17):8834-42
references: 16912331
references: J Gen Virol. 2005 Aug;86(Pt 8):2333-8
references: 16033981
references: PLoS Pathog. 2011 May;7(5):e1002030
references: 21589902
references: J Virol. 2012 Oct;86(20):10914-23
references: 22875964
references: Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19365-70
references: 22084115
references: Curr Opin Microbiol. 2011 Aug;14(4):504-10
references: 21824806
references: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W445-9
references: 20444869
references: Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11769-74
references: 20547879
references: J Virol. 2005 Aug;79(15):10032-9
references: 16014963
references: Clin Microbiol Infect. 2009 Jun;15(6):510-7
references: 19604275
references: Virol J. 2007 Jul 10;4:72
references: 17623082
references: J Virol. 2003 Aug;77(16):8640-9
references: 12885882
references: J Virol. 1995 Feb;69(2):849-55
references: 7815552
references: J Virol. 2012 Nov;86(22):12294-303
references: 22951837
references: Protein Eng. 1997 Feb;10(2):149-58
references: 9089814
references: Science. 2006 Jul 21;313(5785):360-3
references: 16778023
references: Curr Opin Infect Dis. 2007 Oct;20(5):495-500
references: 17762783
references: J Virol. 1988 Aug;62(8):2658-64
references: 2839693
references: J Virol. 2009 Apr;83(8):3762-9
references: 19193794
references: J Gen Virol. 1981 Jul;55(Pt 1):165-78
references: 7299367
references: J Gen Virol. 2004 Oct;85(Pt 10):3059-70
references: 15448369
references: J Biochem. 1988 Dec;104(6):1021-6
references: 3243763
references: EMBO J. 1994 Jul 1;13(13):3158-65
references: 8039508
references: Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):5046-51
references: 22421137
references: J Mol Biol. 1971 Feb 14;55(3):379-400
references: 5551392
references: N Engl J Med. 2011 Apr 21;364(16):1523-32
references: 21410387
references: Virology. 2006 Jun 5;349(2):422-9
references: 16494915
references: FASEB J. 2008 Oct;22(10):3638-47
references: 18614582
references: Comp Immunol Microbiol Infect Dis. 2007 Sep;30(5-6):375-89
references: 17692916
references: J Virol. 2007 Apr;81(7):3198-205
references: 17229712
references: Travel Med Infect Dis. 2010 May;8(3):139-43
references: 20541133