دورية أكاديمية
Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a highly conserved sequence.
| العنوان: | Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a highly conserved sequence. |
|---|---|
| المؤلفون: | Stein DA; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA., Perry ST, Buck MD, Oehmen CS, Fischer MA, Poore E, Smith JL, Lancaster AM, Hirsch AJ, Slifka MK, Nelson JA, Shresta S, Früh K |
| المصدر: | Journal of virology [J Virol] 2011 Oct; Vol. 85 (19), pp. 10154-66. Date of Electronic Publication: 2011 Jul 27. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Antiviral Agents/*administration & dosage , Antiviral Agents/*pharmacology , Dengue/*drug therapy , Dengue Virus/*drug effects , RNA, Small Interfering/*administration & dosage , RNA, Small Interfering/*pharmacology, Animals ; Antibody-Dependent Enhancement ; Biological Products/administration & dosage ; Biological Products/pharmacology ; Body Weight ; Cell Culture Techniques ; Chlorocebus aethiops ; Conserved Sequence ; Dengue/pathology ; Dengue/virology ; Dengue Virus/genetics ; Disease Models, Animal ; Humans ; Mice ; RNA, Small Interfering/genetics ; Rodent Diseases/drug therapy ; Rodent Diseases/pathology ; Rodent Diseases/virology ; Survival Analysis |
| مستخلص: | The dengue viruses (DENVs) exist as numerous genetic strains that are grouped into four antigenically distinct serotypes. DENV strains from each serotype can cause severe disease and threaten public health in tropical and subtropical regions worldwide. No licensed antiviral agent to treat DENV infections is currently available, and there is an acute need for the development of novel therapeutics. We found that a synthetic small interfering RNA (siRNA) (DC-3) targeting the highly conserved 5' cyclization sequence (5'CS) region of the DENV genome reduced, by more than 100-fold, the titers of representative strains from each DENV serotype in vitro. To determine if DC-3 siRNA could inhibit DENV in vivo, an "in vivo-ready" version of DC-3 was synthesized and tested against DENV-2 by using a mouse model of antibody-dependent enhancement of infection (ADE)-induced disease. Compared with the rapid weight loss and 5-day average survival time of the control groups, mice receiving the DC-3 siRNA had an average survival time of 15 days and showed little weight loss for approximately 12 days. DC-3-treated mice also contained significantly less virus than control groups in several tissues at various time points postinfection. These results suggest that exogenously introduced siRNA combined with the endogenous RNA interference processing machinery has the capacity to prevent severe dengue disease. Overall, the data indicate that DC-3 siRNA represents a useful research reagent and has potential as a novel approach to therapeutic intervention against the genetically diverse dengue viruses. |
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| معلومات مُعتمدة: | U54 AI081680 United States AI NIAID NIH HHS; U01AI082196 United States AI NIAID NIH HHS; T32 AI07472 United States AI NIAID NIH HHS; P51 RR000163 United States RR NCRR NIH HHS; RR00163 United States RR NCRR NIH HHS; U54 AI 081680 United States AI NIAID NIH HHS; T32 AI007472 United States AI NIAID NIH HHS; U01 AI082196 United States AI NIAID NIH HHS; R44 AI079898 United States AI NIAID NIH HHS; T32 A1074494 United States PHS HHS; K01 RR000163 United States RR NCRR NIH HHS |
| المشرفين على المادة: | 0 (Antiviral Agents) 0 (Biological Products) 0 (RNA, Small Interfering) |
| تواريخ الأحداث: | Date Created: 20110729 Date Completed: 20111031 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC3196423 |
| DOI: | 10.1128/JVI.05298-11 |
| PMID: | 21795337 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
|---|---|
| DOI: | 10.1128/JVI.05298-11 |