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....
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todo:paper_01663542_v84_n1_p31_Artuso2023-10-03T15:03:52Z Inhibition of Junín virus replication by small interfering RNAs Artuso, M.C. Ellenberg, P.C. Scolaro, L.A. Damonte, E.B. García, C.C. Arenavirus Junín virus Matrix protein RNA interference siRNAs guanine nucleotide binding protein small interfering RNA virus antigen virus RNA animal cell antigen expression article controlled study drug efficacy drug specificity drug targeting genetic transfection human human cell Junin virus nonhuman nucleotide sequence priority journal protein expression RNA interference virus inhibition virus plaque virus replication Animals Arenaviridae Infections Base Sequence Cell Line Cercopithecus aethiops Cricetinae Down-Regulation Junin virus Molecular Sequence Data RNA Interference RNA, Small Interfering Sequence Alignment Vero Cells Virus Replication Arenavirus Junin virus 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. © 2009 Elsevier B.V. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01663542_v84_n1_p31_Artuso |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Arenavirus Junín virus Matrix protein RNA interference siRNAs guanine nucleotide binding protein small interfering RNA virus antigen virus RNA animal cell antigen expression article controlled study drug efficacy drug specificity drug targeting genetic transfection human human cell Junin virus nonhuman nucleotide sequence priority journal protein expression RNA interference virus inhibition virus plaque virus replication Animals Arenaviridae Infections Base Sequence Cell Line Cercopithecus aethiops Cricetinae Down-Regulation Junin virus Molecular Sequence Data RNA Interference RNA, Small Interfering Sequence Alignment Vero Cells Virus Replication Arenavirus Junin virus |
| spellingShingle |
Arenavirus Junín virus Matrix protein RNA interference siRNAs guanine nucleotide binding protein small interfering RNA virus antigen virus RNA animal cell antigen expression article controlled study drug efficacy drug specificity drug targeting genetic transfection human human cell Junin virus nonhuman nucleotide sequence priority journal protein expression RNA interference virus inhibition virus plaque virus replication Animals Arenaviridae Infections Base Sequence Cell Line Cercopithecus aethiops Cricetinae Down-Regulation Junin virus Molecular Sequence Data RNA Interference RNA, Small Interfering Sequence Alignment Vero Cells Virus Replication Arenavirus Junin virus Artuso, M.C. Ellenberg, P.C. Scolaro, L.A. Damonte, E.B. García, C.C. Inhibition of Junín virus replication by small interfering RNAs |
| topic_facet |
Arenavirus Junín virus Matrix protein RNA interference siRNAs guanine nucleotide binding protein small interfering RNA virus antigen virus RNA animal cell antigen expression article controlled study drug efficacy drug specificity drug targeting genetic transfection human human cell Junin virus nonhuman nucleotide sequence priority journal protein expression RNA interference virus inhibition virus plaque virus replication Animals Arenaviridae Infections Base Sequence Cell Line Cercopithecus aethiops Cricetinae Down-Regulation Junin virus Molecular Sequence Data RNA Interference RNA, Small Interfering Sequence Alignment Vero Cells Virus Replication Arenavirus Junin virus |
| description |
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. © 2009 Elsevier B.V. All rights reserved. |
| format |
JOUR |
| author |
Artuso, M.C. Ellenberg, P.C. Scolaro, L.A. Damonte, E.B. García, C.C. |
| author_facet |
Artuso, M.C. Ellenberg, P.C. Scolaro, L.A. Damonte, E.B. García, C.C. |
| author_sort |
Artuso, M.C. |
| title |
Inhibition of Junín virus replication by small interfering RNAs |
| title_short |
Inhibition of Junín virus replication by small interfering RNAs |
| title_full |
Inhibition of Junín virus replication by small interfering RNAs |
| title_fullStr |
Inhibition of Junín virus replication by small interfering RNAs |
| title_full_unstemmed |
Inhibition of Junín virus replication by small interfering RNAs |
| title_sort |
inhibition of junín virus replication by small interfering rnas |
| url |
http://hdl.handle.net/20.500.12110/paper_01663542_v84_n1_p31_Artuso |
| work_keys_str_mv |
AT artusomc inhibitionofjuninvirusreplicationbysmallinterferingrnas AT ellenbergpc inhibitionofjuninvirusreplicationbysmallinterferingrnas AT scolarola inhibitionofjuninvirusreplicationbysmallinterferingrnas AT damonteeb inhibitionofjuninvirusreplicationbysmallinterferingrnas AT garciacc inhibitionofjuninvirusreplicationbysmallinterferingrnas |
| _version_ |
1807319859065782272 |