{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:34:40Z","timestamp":1790472880985,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2009,6,1]],"date-time":"2009-06-01T00:00:00Z","timestamp":1243814400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In view of the threat of the potential use of variola virus in a terrorist attack, considerable efforts have been performed to develop new antiviral strategies against orthopoxviruses. Here we report on the use of RNA interference, either alone or in combination with cidofovir, as an approach to inhibit orthopoxvirus replication. Two selected small interfering RNAs (siRNAs), named siB1R-2 and siG7L-1, and a previously reported siRNA, i.e., siD5R-2 (which targets the viral D5R mRNA), were evaluated for antiviral activity against vaccinia virus (VACV) by plaque reduction and virus yield assays. siB1R-2 and siG7L-1, administered before or after viral infection, reduced VACV replication by more than 90%. Also, these two siRNAs decreased monkeypox virus replication by 95% at a concentration of 1 nM. siB1R-2 and siG7L-1 were demonstrated to specifically silence their corresponding transcripts, i.e., B1R and G7L mRNAs, without induction of a beta interferon response. Strong synergistic effects were observed when siB1R-2, siG7L-1, or siD5R-2 was combined with cidofovir. In addition, the antiviral activities of these three siRNAs were evaluated against VACV resistant to cidofovir and other acyclic nucleoside phosphonates. siG7L-1 and siD5R-2 remained active against four of five VACV mutants, while siB1R-2 showed activity against only one of the mutants. Our results showed that siRNAs are potent inhibitory agents in vitro, not only against wild-type VACV but also against several cidofovir-resistant VACV. Furthermore, we showed that a combined therapy using siRNA and cidofovir may be useful in the treatment of poxvirus infections.<\/jats:p>","DOI":"10.1128\/aac.01626-08","type":"journal-article","created":{"date-parts":[[2009,3,23]],"date-time":"2009-03-23T21:39:47Z","timestamp":1237844387000},"page":"2579-2588","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["Inhibition of Vaccinia Virus Replication by Two Small Interfering RNAs Targeting B1R and G7L Genes and Their Synergistic Combination with Cidofovir"],"prefix":"10.1128","volume":"53","author":[{"given":"Solenne","family":"Vigne","sequence":"first","affiliation":[{"name":"CRSSA Emile Parde\u0301, Virology Laboratory, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Duraffour","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Virology and Chemotherapy Section, K. U. Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciela","family":"Andrei","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Virology and Chemotherapy Section, K. U. Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Snoeck","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Virology and Chemotherapy Section, K. U. Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Garin","sequence":"additional","affiliation":[{"name":"CRSSA Emile Parde\u0301, Virology Laboratory, La Tronche, France"},{"name":"Ecole du Val-de-Gra\u0302ce, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Marc","family":"Crance","sequence":"additional","affiliation":[{"name":"CRSSA Emile Parde\u0301, Virology Laboratory, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1749-6632.1999.tb08038.x","volume":"894","year":"1999","unstructured":"Alibek, K. 1999. The Soviet Union's anti-agricultural biological weapons. Ann. N. Y. Acad. Sci.894:18-19.","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0166-3542(82)90043-2","volume":"2","year":"1982","unstructured":"Allen, L. B., L. K. Vanderslice, C. M. Fingal, F. H. McCright, E. F. Harris, and P. D. Cook. 1982. Evaluation of the anti-herpesvirus drug combinations: virazole plus arabinofuranosylhypoxanthine and virazole plus arabinofuranosyladenine. Antivir. Res.2:203-216.","journal-title":"Antivir. Res."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg147"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00605-06"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.3201\/eid0905.020388","volume":"9","year":"2003","unstructured":"Ashford, D. A., R. M. Kaiser, M. E. Bales, K. Shutt, A. Patrawalla, A. McShan, J. W. Tappero, B. A. Perkins, and A. L. Dannenberg. 2003. Planning against biological terrorism: lessons from outbreak investigations. Emerg. Infect. Dis.9:515-519.","journal-title":"Emerg. Infect. Dis."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711573105"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90256-O"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.it.2005.03.003","volume":"26","year":"2005","unstructured":"Bayry, J., and D. F. Tough. 2005. Is RNA interference feasible for the control of foot-and-mouth disease outbreaks? Trends Immunol.26:238-239.","journal-title":"Trends Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-1-34"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1164"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.4.1992-2005.2004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.antiviral.2003.09.005","volume":"61","year":"2004","unstructured":"Briolant, S., D. Garin, N. Scaramozzino, A. Jouan, and J. M. Crance. 2004. Inhibition of Chikungunya and Semliki Forest viruses replication by antiviral compounds: synergistic effect of interferon-alpha and ribavirin combination. Antivir. Res.61:111-117.","journal-title":"Antivir. Res."},{"key":"e_1_3_2_14_2","first-page":"1","volume":"52","year":"2003","unstructured":"Cono, J., C. G. Casey, and D. M. Bell. 2003. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Recomm. Rep.52:1-28.","journal-title":"MMWR Recomm. Rep."},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1093\/nar\/gkn190","volume":"36","year":"2008","unstructured":"Dahlgren, C., H. Y. Zhang, Q. Du, M. Grahn, G. Norstedt, C. Wahlestedt, and Z. Liang. 2008. Analysis of siRNA specificity on targets with double-nucleotide mismatches. Nucleic Acids Res.36:e53.","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.013"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(02)00008-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.antiviral.2007.11.009","volume":"77","year":"2008","unstructured":"DeVincenzo, J., J. E. Cehelsky, R. Alvarez, S. Elbashir, J. Harborth, I. Toudjarska, L. Nechev, V. Murugaiah, A. Van Vliet, A. K. Vaishnaw, and R. Meyers. 2008. Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV). Antivir. Res.77:225-231.","journal-title":"Antivir. Res."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki312"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00838-07"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.862301"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)65573-5"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.61.10.3152-3162.1987"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jhin.2004.01.012","volume":"57","year":"2004","unstructured":"Ferrier, A., D. Garin, and J. M. Crance. 2004. Rapid inactivation of vaccinia virus in suspension and dried on surfaces. J. Hosp. Infect.57:73-79.","journal-title":"J. Hosp. Infect."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.11.4097-4102.2004"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01528-08"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402486101"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/504267"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00244-2"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/11.5.427"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00400-9"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00896"},{"key":"e_1_3_2_33_2","first-page":"203","volume":"7","year":"1967","unstructured":"Jawetz, E. 1967. Combined antibiotic action: some definitions and correlations between laboratory and clinical results. Antimicrob. Agents Chemother.7:203-209.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01303-07"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nbt1081","volume":"23","year":"2005","unstructured":"Judge, A. D., V. Sood, J. R. Shaw, D. Fang, K. McClintock, and I. MacLachlan. 2005. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat. Biotechnol.23:457-462.","journal-title":"Nat. Biotechnol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00380-06"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.034"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/44.2.97"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-126-4-199702150-00001"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1280"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.49.2.510-520.1984"},{"key":"e_1_3_2_42_2","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1101\/gad.1187904","volume":"18","year":"2004","unstructured":"Martinez, J., and T. Tuschl. 2004. RISC is a 5\u2032 phosphomonoester-producing RNA endonuclease. Genes Dev.18:975-980.","journal-title":"Genes Dev."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/418038a"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt824"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.7146-7161.2005"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20702"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1122"},{"key":"e_1_3_2_48_2","first-page":"2849","volume":"2","year":"2001","unstructured":"Moss, B. 2001. Poxviridae: the viruses and their replication, p. 2849-2883. In D. M. Knipe and P. M. Howley (ed.), Fields virology, 4th ed., vol. 2. Lippincott Williams & Wilkins, Philadelphia, PA.","journal-title":"Fields virology"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/35060032"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01299-07"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-12-1179"},{"key":"e_1_3_2_52_2","first-page":"102","volume":"3","year":"2008","unstructured":"Nikonenko, B. V., K. A. Sacksteder, S. Hundert, L. Einck, and C. A. Nacy. 2008. Preclinical study of new TB drugs and drug combinations in mouse models. Recent Patents Anti-Infect. Drug Discov.3:102-116.","journal-title":"Drug Discov."},{"key":"e_1_3_2_53_2","first-page":"26","volume":"3","year":"1998","unstructured":"Orent, W. 1998. Escape from Moscow. Sciences3:26-31.","journal-title":"Sciences"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04263"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00879-06"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.2.574-583.1990"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.7.4413-4426.1992"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.08.013"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1468-1471.2003"},{"key":"e_1_3_2_60_2","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/j.1365-2672.2004.02417.x","volume":"97","year":"2004","unstructured":"Shin, S., and S. Lim. 2004. Antifungal effects of herbal essential oils alone and in combination with ketoconazole against Trichophyton spp. J. Appl. Microbiol.97:1289-1296.","journal-title":"J. Appl. Microbiol."},{"key":"e_1_3_2_61_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/biot.200700215","volume":"3","year":"2008","unstructured":"Shrivastava, N., and A. Srivastava. 2008. RNA interference: an emerging generation of biologicals. Biotechnol. J.3:339-353.","journal-title":"Biotechnol. J."},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1038"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.5.1329-1335.2002"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.13.7174-7181.2003"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.6.3418-3429.2003"},{"key":"e_1_3_2_66_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0014-2964(73)80023-4","volume":"9","year":"1973","unstructured":"Tattersall, M. H., and K. R. Harrap. 1973. Combination chemotherapy: the antagonism of methotrexate and cytosine arabinoside. Eur. J. Cancer9:229-232.","journal-title":"Eur. J. Cancer"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402630101"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1122411"},{"key":"e_1_3_2_69_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/135965350801300307","volume":"13","year":"2008","unstructured":"Vigne, S., R. Germi, S. Duraffour, S. Larrat, G. Andrei, R. Snoeck, D. Garin, and J. M. Crance. 2008. Specific inhibition of orthopoxvirus replication by a small interfering RNA targeting the D5R gene. Antivir. Ther.13:357-368.","journal-title":"Antivir. Ther."},{"key":"e_1_3_2_70_2","unstructured":"Abstr. 17th Int. Poxvirus Iridovirus Conf. 2008"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.8.1914"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.03.007"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.13139-13149.2005"},{"key":"e_1_3_2_74_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.antiviral.2006.05.022","volume":"73","year":"2007","unstructured":"Ying, R. S., C. Zhu, X. G. Fan, N. Li, X. F. Tian, H. B. Liu, and B. X. Zhang. 2007. Hepatitis B virus is inhibited by RNA interference in cell culture and in mice. Antivir. Res.73:24-30.","journal-title":"Antivir. Res."},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1174"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01626-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01626-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T11:41:52Z","timestamp":1684928512000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01626-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6]]},"references-count":74,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,6]]}},"alternative-id":["10.1128\/AAC.01626-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.01626-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6]]},"assertion":[{"value":"2008-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-03-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}