Inhibition of Junín virus replication by small interfering RNAs.
Junín virus (JUNV), the etiological agent of the Argentine hemorrhagic fever, has a single-stranded RNA genome with ambisense expression which encodes for five proteins. In previous works we have demonstrated that the Z arenavirus matrix protein represents an attractive target for antiviral therapy. With the aim of studying a new alternative therapeutic mechanism, four Z-specific siRNAs (Z1- to Z4-siRNAs) were tested showing variable efficacy. The most effective inhibitor was Z2-siRNA targeted at the region encompassed by nt 179-197 of Z gene. The efficacy of this Z2-siRNA against JUNV was also demonstrated in virus-infected cells, by testing infectious virus plaque formation (92.8% JUNV yield reduction), viral RNA level or antigen expression, as well as in cells transfected with Z-specific reporter plasmids (91% reduction in expression of Z-EGFP fusion protein). Furthermore, the lack of effect of this Z-siRNA on the expression of other JUNV proteins, such as N and GPC, confirmed the specificity of action exerted by Z2-siRNA on Z transcript. Thus, the present study represents the first report of virus inhibition mediated by RNA interference for a New World arenavirus.
Artuso
María C
MC
Laboratory of Virology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina.
Ellenberg
Paula C
PC
Scolaro
Luis A
LA
Damonte
Elsa B
EB
García
Cybele C
CC
D000818:Animals; D001117:Arenaviridae Infections / Q000821:virology*; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D015536:Down-Regulation; D018051:Junin virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014709:Vero Cells; D014779:Virus Replication
D034741:RNA, Small Interfering