title: RNA interference against animal viruses: how morbilliviruses generate extended diversity to escape small interfering RNA control.
abstract: Viruses are serious threats to human and animal health. Vaccines can prevent viral diseases, but few antiviral treatments are available to control evolving infections. Among new antiviral therapies, RNA interference (RNAi) has been the focus of intensive research. However, along with the development of efficient RNAi-based therapeutics comes the risk of emergence of resistant viruses. In this study, we challenged the in vitro propensity of a morbillivirus (peste des petits ruminants virus), a stable RNA virus, to escape the inhibition conferred by single or multiple small interfering RNAs (siRNAs) against conserved regions of the N gene. Except with the combination of three different siRNAs, the virus systematically escaped RNAi after 3 to 20 consecutive passages. The genetic modifications involved consisted of single or multiple point nucleotide mutations and a deletion of a stretch of six nucleotides, illustrating that this virus has an unusual genomic malleability.
authors.affiliation: UMR CMAEE, CIRAD, F-34398 Montpellier, France.
authors.forename: Carine L
authors.initials: CL
authors.lastname: Holz
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Albina
authors.forename: Cécile
authors.initials: C
authors.lastname: Minet
authors.forename: Renaud
authors.initials: R
authors.lastname: Lancelot
authors.forename: Olivier
authors.initials: O
authors.lastname: Kwiatek
authors.forename: Geneviève
authors.initials: G
authors.lastname: Libeau
authors.forename: Renata
authors.initials: R
authors.lastname: Servan de Almeida
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D019590:Nucleocapsid Proteins / Q000235:genetics / Q000378:metabolism; D029021:Peste-des-Petits-Ruminants / Q000188:drug therapy / Q000821:virology*; D018107:Peste-des-petits-ruminants virus / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D019590:Nucleocapsid Proteins; D034741:RNA, Small Interfering
references.citation: J Virol. 2003 Nov;77(21):11531-5
references.pmid: 14557638
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12411-2
references.pmid: 11035785
references.citation: Lancet. 1998 Feb 14;351(9101):472-7
references.pmid: 9482438
references.citation: Biochem Biophys Res Commun. 2004 May 28;318(2):341-5
references.pmid: 15120607
references.citation: Vet Microbiol. 1995 May;44(2-4):127-34
references.pmid: 8588306
references.citation: Drug Discov Today. 2006 Jan;11(1-2):67-73
references.pmid: 16478693
references.citation: J Virol. 2004 Apr;78(7):3436-46
references.pmid: 15016866
references.citation: Microbes Infect. 2005 Apr;7(4):767-75
references.pmid: 15820151
references.citation: J Virol. 2005 Jun;79(11):7050-8
references.pmid: 15890944
references.citation: J Mol Evol. 2002 Feb;54(2):156-65
references.pmid: 11821909
references.citation: Emerg Infect Dis. 2004 Sep;10(9):1688-9
references.pmid: 15503405
references.citation: Nucleic Acids Res. 2005 Feb 01;33(2):796-804
references.pmid: 15687388
references.citation: Nature. 2002 Jul 25;418(6896):435-8
references.pmid: 12087358
references.citation: Nature. 2009 Jan 22;457(7228):426-33
references.pmid: 19158789
references.citation: Methods Mol Biol. 2009;487:83-92
references.pmid: 19301643
references.citation: CMAJ. 2004 Nov 23;171(11):1342-4
references.pmid: 15557583
references.citation: BMC Evol Biol. 2004 Jun 28;4:18
references.pmid: 15222900
references.citation: J Gen Virol. 1994 Jan;75 ( Pt 1):233-7
references.pmid: 8113734
references.citation: Rev Med Virol. 2003 Nov-Dec;13(6):373-85
references.pmid: 14625885
references.citation: Nature. 2001 May 24;411(6836):494-8
references.pmid: 11373684
references.citation: J Viral Hepat. 2006 Nov;13(11):756-61
references.pmid: 17052275
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Bioinformatics. 2001 Aug;17(8):754-5
references.pmid: 11524383
references.citation: J Virol. 2004 Mar;78(5):2601-5
references.pmid: 14963165
references.citation: Nucleic Acids Res. 2008 May;36(9):2811-24
references.pmid: 18346971
references.citation: J Gen Virol. 2007 Aug;88(Pt 8):2307-2311
references.pmid: 17622636
references.citation: Virol J. 2010 Mar 04;7:52
references.pmid: 20202190
references.citation: BMC Evol Biol. 2007 Nov 08;7:214
references.pmid: 17996036
references.citation: Science. 2002 May 17;296(5571):1263-5
references.pmid: 12016302
references.citation: Nature. 1998 Feb 19;391(6669):806-11
references.pmid: 9486653
references.citation: J Virol. 2006 Jun;80(11):5599-610
references.pmid: 16699041
references.citation: Prev Vet Med. 2008 Oct 15;87(1-2):21-30
references.pmid: 18620767
references.citation: Antiviral Res. 2007 Apr;74(1):77-81
references.pmid: 17275932
references.citation: RNA. 2009 May;15(5):898-910
references.pmid: 19324960
references.citation: Virus Res. 2008 Mar;132(1-2):213-9
references.pmid: 18166241
references.citation: Virologie (Montrouge). 2005 Feb 1;9(1):19-34
references.pmid: 34479437
references.citation: Nat Biotechnol. 2007 Dec;25(12):1435-43
references.pmid: 18066040
references.citation: J Virol. 2008 Mar;82(6):2895-903
references.pmid: 18077712
references.citation: Rev Elev Med Vet Pays Trop. 1989;42(3):311-9
references.pmid: 2485537
references.citation: Handb Exp Pharmacol. 2006;(173):117-50
references.pmid: 16594614
references.citation: Antiviral Res. 2008 Nov;80(2):158-67
references.pmid: 18634829
references.citation: Science. 2001 Oct 26;294(5543):813-7
references.pmid: 11679661
references.citation: J Virol. 2006 Jun;80(12):5951-7
references.pmid: 16731933
references.citation: Gastroenterology. 2005 Mar;128(3):708-16
references.pmid: 15765406
references.citation: J Virol. 2006 Jan;80(2):571-7
references.pmid: 16378959
references.citation: Comput Appl Biosci. 1996 Dec;12(6):543-8
references.pmid: 9021275
references.citation: Hum Gene Ther. 2008 Feb;19(2):125-32
references.pmid: 18257677
references.citation: Mol Biol Evol. 2010 Feb;27(2):221-4
references.pmid: 19854763
references.citation: RNA. 1996 Oct;2(10):1033-45
references.pmid: 8849779