Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral▿
Identifieur interne : 000299 ( Ncbi/Merge ); précédent : 000298; suivant : 000300Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral▿
Auteurs : Nigel J. Dimmock [Royaume-Uni] ; Edward W. Rainsford [Royaume-Uni] ; Paul D. Scott [Royaume-Uni] ; Anthony C. Marriott [Royaume-Uni]Source :
- Journal of Virology [ 0022-538X ] ; 2008.
Descripteurs français
- KwdFr :
- ARN viral (analyse), ARN viral (usage thérapeutique), Animaux, Antiviraux (usage thérapeutique), Dose létale 50, Facteurs temps, Humains, Indice de gravité médicale, Infections à Orthomyxoviridae (), Lignée cellulaire, Perte de poids, Plasmides, Rein (cytologie), Souris, Souris de lignée C3H, Sous-type H1N1 du virus de la grippe A (physiologie), Sous-type H2N2 du virus de la grippe A (physiologie), Sous-type H3N2 du virus de la grippe A (physiologie), Sous-type H3N8 du virus de la grippe A (physiologie), Transfection, Virus assistants (physiologie), Virus de la grippe A (physiologie), Virus défectifs (physiologie).
- MESH :
- analyse : ARN viral.
- cytologie : Rein.
- physiologie : Sous-type H1N1 du virus de la grippe A, Sous-type H2N2 du virus de la grippe A, Sous-type H3N2 du virus de la grippe A, Sous-type H3N8 du virus de la grippe A, Virus assistants, Virus de la grippe A, Virus défectifs.
- usage thérapeutique : ARN viral, Antiviraux.
- Animaux, Dose létale 50, Facteurs temps, Humains, Indice de gravité médicale, Infections à Orthomyxoviridae, Lignée cellulaire, Perte de poids, Plasmides, Souris, Souris de lignée C3H, Transfection.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (therapeutic use), Cell Line, Defective Viruses (physiology), Helper Viruses (physiology), Humans, Influenza A Virus, H1N1 Subtype (physiology), Influenza A Virus, H2N2 Subtype (physiology), Influenza A Virus, H3N2 Subtype (physiology), Influenza A Virus, H3N8 Subtype (physiology), Influenza A virus (physiology), Kidney (cytology), Lethal Dose 50, Mice, Mice, Inbred C3H, Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (therapy), Plasmids, RNA, Viral (analysis), RNA, Viral (therapeutic use), Severity of Illness Index, Time Factors, Transfection, Weight Loss.
- MESH :
- chemical , analysis : RNA, Viral.
- chemical , therapeutic use : Antiviral Agents, RNA, Viral.
- cytology : Kidney.
- physiology : Defective Viruses, Helper Viruses, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H2N2 Subtype, Influenza A Virus, H3N2 Subtype, Influenza A Virus, H3N8 Subtype, Influenza A virus.
- prevention & control : Orthomyxoviridae Infections.
- therapy : Orthomyxoviridae Infections.
- Animals, Cell Line, Humans, Lethal Dose 50, Mice, Mice, Inbred C3H, Plasmids, Severity of Illness Index, Time Factors, Transfection, Weight Loss.
Abstract
Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This “protecting RNA” (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.
Url:
DOI: 10.1128/JVI.00743-08
PubMed: 18579602
PubMed Central: 2519629
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PMC:2519629Le document en format XML
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Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This “protecting RNA” (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.</p></div></front></TEI><double pmid="18579602"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Dimmock, Nigel J" sort="Dimmock, Nigel J" uniqKey="Dimmock N" first="Nigel J." last="Dimmock">Nigel J. Dimmock</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Rainsford, Edward W" sort="Rainsford, Edward W" uniqKey="Rainsford E" first="Edward W." last="Rainsford">Edward W. Rainsford</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Scott, Paul D" sort="Scott, Paul D" uniqKey="Scott P" first="Paul D." last="Scott">Paul D. Scott</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Marriott, Anthony C" sort="Marriott, Anthony C" uniqKey="Marriott A" first="Anthony C." last="Marriott">Anthony C. Marriott</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18579602</idno><idno type="pmc">2519629</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519629</idno><idno type="RBID">PMC:2519629</idno><idno type="doi">10.1128/JVI.00743-08</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000361</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000361</idno><idno type="wicri:Area/Pmc/Curation">000361</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000361</idno><idno type="wicri:Area/Pmc/Checkpoint">000B14</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000B14</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral<xref ref-type="fn" rid="fn2">▿</xref> </title><author><name sortKey="Dimmock, Nigel J" sort="Dimmock, Nigel J" uniqKey="Dimmock N" first="Nigel J." last="Dimmock">Nigel J. Dimmock</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Rainsford, Edward W" sort="Rainsford, Edward W" uniqKey="Rainsford E" first="Edward W." last="Rainsford">Edward W. Rainsford</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Scott, Paul D" sort="Scott, Paul D" uniqKey="Scott P" first="Paul D." last="Scott">Paul D. Scott</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author><author><name sortKey="Marriott, Anthony C" sort="Marriott, Anthony C" uniqKey="Marriott A" first="Anthony C." last="Marriott">Anthony C. Marriott</name><affiliation wicri:level="1"><nlm:aff id="aff0">Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry CV4 7AL</wicri:regionArea><wicri:noRegion>Coventry CV4 7AL</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Virology</title><idno type="ISSN">0022-538X</idno><idno type="eISSN">1098-5514</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This “protecting RNA” (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral.</title><author><name sortKey="Dimmock, Nigel J" sort="Dimmock, Nigel J" uniqKey="Dimmock N" first="Nigel J" last="Dimmock">Nigel J. Dimmock</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry</wicri:regionArea><wicri:noRegion>Coventry</wicri:noRegion></affiliation></author><author><name sortKey="Rainsford, Edward W" sort="Rainsford, Edward W" uniqKey="Rainsford E" first="Edward W" last="Rainsford">Edward W. Rainsford</name></author><author><name sortKey="Scott, Paul D" sort="Scott, Paul D" uniqKey="Scott P" first="Paul D" last="Scott">Paul D. Scott</name></author><author><name sortKey="Marriott, Anthony C" sort="Marriott, Anthony C" uniqKey="Marriott A" first="Anthony C" last="Marriott">Anthony C. Marriott</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:18579602</idno><idno type="pmid">18579602</idno><idno type="doi">10.1128/JVI.00743-08</idno><idno type="wicri:Area/PubMed/Corpus">000257</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000257</idno><idno type="wicri:Area/PubMed/Curation">000257</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000257</idno><idno type="wicri:Area/PubMed/Checkpoint">000232</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000232</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Influenza virus protecting RNA: an effective prophylactic and therapeutic antiviral.</title><author><name sortKey="Dimmock, Nigel J" sort="Dimmock, Nigel J" uniqKey="Dimmock N" first="Nigel J" last="Dimmock">Nigel J. Dimmock</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biological Sciences, University of Warwick, Coventry, United Kingdom.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Biological Sciences, University of Warwick, Coventry</wicri:regionArea><wicri:noRegion>Coventry</wicri:noRegion></affiliation></author><author><name sortKey="Rainsford, Edward W" sort="Rainsford, Edward W" uniqKey="Rainsford E" first="Edward W" last="Rainsford">Edward W. Rainsford</name></author><author><name sortKey="Scott, Paul D" sort="Scott, Paul D" uniqKey="Scott P" first="Paul D" last="Scott">Paul D. Scott</name></author><author><name sortKey="Marriott, Anthony C" sort="Marriott, Anthony C" uniqKey="Marriott A" first="Anthony C" last="Marriott">Anthony C. Marriott</name></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (therapeutic use)</term><term>Cell Line</term><term>Defective Viruses (physiology)</term><term>Helper Viruses (physiology)</term><term>Humans</term><term>Influenza A Virus, H1N1 Subtype (physiology)</term><term>Influenza A Virus, H2N2 Subtype (physiology)</term><term>Influenza A Virus, H3N2 Subtype (physiology)</term><term>Influenza A Virus, H3N8 Subtype (physiology)</term><term>Influenza A virus (physiology)</term><term>Kidney (cytology)</term><term>Lethal Dose 50</term><term>Mice</term><term>Mice, Inbred C3H</term><term>Orthomyxoviridae Infections (prevention & control)</term><term>Orthomyxoviridae Infections (therapy)</term><term>Plasmids</term><term>RNA, Viral (analysis)</term><term>RNA, Viral (therapeutic use)</term><term>Severity of Illness Index</term><term>Time Factors</term><term>Transfection</term><term>Weight Loss</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ARN viral (analyse)</term><term>ARN viral (usage thérapeutique)</term><term>Animaux</term><term>Antiviraux (usage thérapeutique)</term><term>Dose létale 50</term><term>Facteurs temps</term><term>Humains</term><term>Indice de gravité médicale</term><term>Infections à Orthomyxoviridae ()</term><term>Lignée cellulaire</term><term>Perte de poids</term><term>Plasmides</term><term>Rein (cytologie)</term><term>Souris</term><term>Souris de lignée C3H</term><term>Sous-type H1N1 du virus de la grippe A (physiologie)</term><term>Sous-type H2N2 du virus de la grippe A (physiologie)</term><term>Sous-type H3N2 du virus de la grippe A (physiologie)</term><term>Sous-type H3N8 du virus de la grippe A (physiologie)</term><term>Transfection</term><term>Virus assistants (physiologie)</term><term>Virus de la grippe A (physiologie)</term><term>Virus défectifs (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>RNA, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term><term>RNA, Viral</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>ARN viral</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Rein</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Kidney</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Sous-type H1N1 du virus de la grippe A</term><term>Sous-type H2N2 du virus de la grippe A</term><term>Sous-type H3N2 du virus de la grippe A</term><term>Sous-type H3N8 du virus de la grippe A</term><term>Virus assistants</term><term>Virus de la grippe A</term><term>Virus défectifs</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Defective Viruses</term><term>Helper Viruses</term><term>Influenza A Virus, H1N1 Subtype</term><term>Influenza A Virus, H2N2 Subtype</term><term>Influenza A Virus, H3N2 Subtype</term><term>Influenza A Virus, H3N8 Subtype</term><term>Influenza A virus</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Orthomyxoviridae Infections</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>ARN viral</term><term>Antiviraux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Humans</term><term>Lethal Dose 50</term><term>Mice</term><term>Mice, Inbred C3H</term><term>Plasmids</term><term>Severity of Illness Index</term><term>Time Factors</term><term>Transfection</term><term>Weight Loss</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Dose létale 50</term><term>Facteurs temps</term><term>Humains</term><term>Indice de gravité médicale</term><term>Infections à Orthomyxoviridae</term><term>Lignée cellulaire</term><term>Perte de poids</term><term>Plasmides</term><term>Souris</term><term>Souris de lignée C3H</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This "protecting RNA" (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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