Home LiteratureArticle Details
PMID: 15173599 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of influenza virus production in virus-infected mice by RNA interference.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 23 ·2004-06-08 ·Pages 8676-81

Ge Q, Filip L, Bai A, Nguyen T, Eisen HN, Chen J

Abstract

Influenza A virus infection is a major source of morbidity and mortality worldwide. Because the effectiveness of existing vaccines and antiviral drugs is limited, development of new treatment modalities is needed. Here, we show that short interfering RNAs (siRNAs) specific for conserved regions of influenza virus genes can prevent and treat influenza virus infection in mice. Virus production in lungs of infected mice is reduced by siRNAs given either before or after initiating virus infection, by using slow i.v. administration of small volumes containing siRNAs in complexes with a polycation carrier. Similar effects also are observed when mice are given DNA vectors i.v. or intranasally, from which siRNA precursors can be transcribed. Development of delivery systems that may be compatible with human use demonstrates the potential utility of siRNAs for prophylaxis and therapy of influenza virus infections in humans.

MeSH Terms
Animals Genes, Viral Genetic Vectors Humans Influenza A virus/genetics,physiology Influenza, Human/immunology,prevention & control,therapy,virology Injections, Intravenous Male Mice Mice, Inbred C57BL Polyethyleneimine RNA Interference RNA, Small Interfering/administration & dosage,genetics Virus Replication
Chemicals
RNA, Small Interfering Polyethyleneimine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Ge Qing
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Filip Lily
Bai Ailin
Nguyen Tam
Eisen Herman N
Chen Jianzhu
References (41)
41 references, click to expand
  1. Polyethylenimine shows properties of interest for cystic fibrosis gene therapy.
    Biochim Biophys Acta. 1999 Oct 28;1447(2-3):219-25 PMID: 10542318
  2. Polyethylenimine-based intravenous delivery of transgenes to mouse lung.
    Gene Ther. 1998 Sep;5(9):1291-5 PMID: 9930332
  3. Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes.
    Gene Ther. 2000 Mar;7(6):499-504 PMID: 10757023
  4. Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse.
    J Gene Med. 2000 Mar-Apr;2(2):128-34 PMID: 10809146
  5. Development of biomaterials for gene therapy.
    Mol Ther. 2000 Oct;2(4):302-17 PMID: 11020345
  6. RNA interference--2001.
    Genes Dev. 2001 Mar 1;15(5):485-90 PMID: 11238371
  7. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells.
    Nature. 2001 May 24;411(6836):494-8 PMID: 11373684
  8. Post-transcriptional gene silencing in plants.
    J Cell Sci. 2001 Sep;114(Pt 17):3083-91 PMID: 11590235
  9. A system for stable expression of short interfering RNAs in mammalian cells.
    Science. 2002 Apr 19;296(5567):550-3 PMID: 11910072
  10. Antisense-RNA regulation and RNA interference.
    Biochim Biophys Acta. 2002 May 3;1575(1-3):15-25 PMID: 12020814
  11. Comparison of surfactant and perfluorochemical liquid enhanced adenovirus-mediated gene transfer in normal rat lung.
    Mol Ther. 2002 Jul;6(1):43-9 PMID: 12095302
  12. RNA interference in adult mice.
    Nature. 2002 Jul 4;418(6893):38-9 PMID: 12097900
  13. DNA vaccine expressing conserved influenza virus proteins protective against H5N1 challenge infection in mice.
    Emerg Infect Dis. 2002 Aug;8(8):796-801 PMID: 12141964
  14. Efficient delivery of siRNA for inhibition of gene expression in postnatal mice.
    Nat Genet. 2002 Sep;32(1):107-8 PMID: 12145662
  15. Phenotypic silencing of cytoplasmic genes using sequence-specific double-stranded short interfering RNA and its application in the reverse genetics of wild type negative-strand RNA viruses.
    BMC Microbiol. 2001;1:34 PMID: 11801185
  16. RNA interference: a promising approach to antiviral therapy?
    Trends Mol Med. 2002 Nov;8(11):505-8 PMID: 12421679
  17. The treatment of influenza with antiviral drugs.
    CMAJ. 2003 Jan 7;168(1):49-56 PMID: 12515786
  18. Mortality associated with influenza and respiratory syncytial virus in the United States.
    JAMA. 2003 Jan 8;289(2):179-86 PMID: 12517228
  19. Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):235-40 PMID: 12518066
  20. Interference of hepatitis C virus RNA replication by short interfering RNAs.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2014-8 PMID: 12566571
  21. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference.
    Nat Genet. 2003 Mar;33(3):401-6 PMID: 12590264
  22. RNA interference targeting Fas protects mice from fulminant hepatitis.
    Nat Med. 2003 Mar;9(3):347-51 PMID: 12579197
  23. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription.
    Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2718-23 PMID: 12594334
  24. Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs.
    EMBO Rep. 2003 Jun;4(6):602-8 PMID: 12740604
  25. Genomewide view of gene silencing by small interfering RNAs.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6343-6 PMID: 12730368
  26. Specificity of short interfering RNA determined through gene expression signatures.
    Proc Natl Acad Sci U S A. 2003 May 27;100(11):6347-52 PMID: 12746500
  27. Inhibition of hepatitis B virus in mice by RNA interference.
    Nat Biotechnol. 2003 Jun;21(6):639-44 PMID: 12740585
  28. Human viruses under attack by small inhibitory RNA.
    Trends Microbiol. 2003 Aug;11(8):345-7 PMID: 12915090
  29. Activation of the interferon system by short-interfering RNAs.
    Nat Cell Biol. 2003 Sep;5(9):834-9 PMID: 12942087
  30. The utility of siRNA transcripts produced by RNA polymerase i in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses.
    Virology. 2003 Sep 1;313(2):514-24 PMID: 12954218
  31. Inhibition of human immunodeficiency virus type 1 replication in primary macrophages by using Tat- or CCR5-specific small interfering RNAs expressed from a lentivirus vector.
    J Virol. 2003 Nov;77(22):11964-72 PMID: 14581533
  32. Nonspecific, concentration-dependent stimulation and repression of mammalian gene expression by small interfering RNAs (siRNAs).
    RNA. 2004 Jan;10(1):12-8 PMID: 14681580
  33. Interferon induction by siRNAs and ssRNAs synthesized by phage polymerase.
    Nat Biotechnol. 2004 Mar;22(3):321-5 PMID: 14990954
  34. Protection against lethal influenza virus challenge by RNA interference in vivo.
    Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8682-6 PMID: 15173583
  35. Efficacy of influenza vaccine in nursing homes. Reduction in illness and complications during an influenza A (H3N2) epidemic.
    JAMA. 1985 Feb 22;253(8):1136-9 PMID: 3968844
  36. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978-1981.
    Am Rev Respir Dis. 1987 Sep;136(3):550-5 PMID: 3631727
  37. The geography and mortality of the 1918 influenza pandemic.
    Bull Hist Med. 1991 Spring;65(1):4-21 PMID: 2021692
  38. Heterosubtypic immunity to influenza type A virus in mice. Effector mechanisms and their longevity.
    J Immunol. 1994 Feb 15;152(4):1653-61 PMID: 8120375
  39. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.
    Nature. 1998 Feb 19;391(6669):806-11 PMID: 9486653
  40. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens.
    Arch Intern Med. 1998 Sep 14;158(16):1769-76 PMID: 9738606
  41. Comparison between cationic polymers and lipids in mediating systemic gene delivery to the lungs.
    Gene Ther. 1999 Dec;6(12):1995-2004 PMID: 10637451
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0402486101
Published
2004-06-08
Epub
2004-00-01
Pages
8676-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC423254
Subset
IM
Grants
NIAID NIH HHS · AI56267 · United States
NCI NIH HHS · R01 CA060686 · United States
NCI NIH HHS · CA60686 · United States
NIAID NIH HHS · AI50631 · United States
NIAID NIH HHS · R01 AI050631 · United States
NIAID NIH HHS · R01 AI056267 · United States
External Links
PubMed source DOI: 10.1073/pnas.0402486101 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2