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dc.contributor.authorSmee, Donald F
dc.contributor.authorvon Itzstein, Mark
dc.contributor.authorBhatt, Beenu
dc.contributor.authorTarbet, E Bart
dc.date.accessioned2017-05-03T15:55:50Z
dc.date.available2017-05-03T15:55:50Z
dc.date.issued2012
dc.date.modified2013-06-17T03:26:03Z
dc.identifier.issn0066-4804
dc.identifier.doi10.1128/AAC.01664-12
dc.identifier.urihttp://hdl.handle.net/10072/48302
dc.description.abstractCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100-1,000 fold lower than infections without such treatment and still cause equivalent mortality. We found intranasal liquid treatments to facilitate virus production (probably through enhanced virus spread) and lung pneumonia that was delayed by only two days relative to a 1000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90-100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death, although the time to death was significantly delayed. A related compound, Neu5Ac2en, was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70-100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1-10 and 30-100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by intranasal route require consideration of both virus challenge dose and virus strain in order to not overwhelm the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society of Microbiology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom6328
dc.relation.ispartofpageto6333
dc.relation.ispartofissue12
dc.relation.ispartofjournalAntimicrobial Agents and Chemotherapy
dc.relation.ispartofvolume56
dc.rights.retentionY
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchVirology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode310706
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode3214
dc.titleExacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.date.issued2012
gro.hasfulltextNo Full Text
gro.griffith.authorvon Itzstein, Mark


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