Document Detail


Inhibition of influenza A H3N8 virus infections in mice by morpholino oligomers.
MedLine Citation:
PMID:  18369525     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
New methods to combat influenza A virus (FLUAV) in humans and animals are needed. The H3N8 subtype virus was the cause of the pandemic of 1890 and has recently undergone cross-species transmission from horses to dogs in the USA. In 2007 H3N8 spread to Australia, a continent previously devoid of equine influenza. Here, we show that antisense-peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs), delivered by intranasal administration, are able to inhibit the replication of FLUAV A/Eq/Miami/1/63 (H3N8) in mice by over 95% compared to controls. Monitoring of body weight and immune cell infiltrates in the lungs of noninfected mice indicated that PPMO treatment was not toxic at a concentration shown to be effectively antiviral in vivo. In addition, we detected a naturally occurring mutation within the PPMO target site of a viral gene that may be the cause of resistance to one of the two antisense PPMO sequences tested. These data indicate that PPMOs targeting highly conserved regions of FLUAV are promising novel therapeutic candidates.
Authors:
Christopher Lupfer; David A Stein; Dan V Mourich; Samuel E Tepper; Patrick L Iversen; Manoj Pastey
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Publication Detail:
Type:  Journal Article     Date:  2008-03-28
Journal Detail:
Title:  Archives of virology     Volume:  153     ISSN:  0304-8608     ISO Abbreviation:  Arch. Virol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-04-18     Completed Date:  2008-07-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7506870     Medline TA:  Arch Virol     Country:  Austria    
Other Details:
Languages:  eng     Pagination:  929-37     Citation Subset:  IM    
Affiliation:
Genetics Program, College of Agricultural Science, Oregon State University, Corvallis, OR 97331, USA.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/EU236678;  EU236679
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MeSH Terms
Descriptor/Qualifier:
Administration, Intranasal
Animals
Base Sequence
Female
Genes, Viral
Influenza A Virus, H3N8 Subtype / drug effects*,  genetics*
Influenza Vaccines / administration & dosage,  genetics,  pharmacology*
Lung / virology
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Nucleoproteins / genetics
Oligodeoxyribonucleotides, Antisense / administration & dosage,  genetics*,  pharmacology*
Orthomyxoviridae Infections / prevention & control*,  virology
RNA, Viral / genetics
RNA-Binding Proteins / genetics
Viral Core Proteins / genetics
Viral Proteins / genetics
Chemical
Reg. No./Substance:
0/Influenza Vaccines; 0/NP protein, Influenza A virus; 0/Nucleoproteins; 0/Oligodeoxyribonucleotides, Antisense; 0/RNA, Viral; 0/RNA-Binding Proteins; 0/Viral Core Proteins; 0/Viral Proteins; 0/influenza virus polymerase basic protein 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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