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Article: Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia

TitleFatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia
Authors
Issue Date2006
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nm
Citation
Nature Medicine, 2006, v. 12 n. 10, p. 1203-1207 How to Cite?
AbstractAvian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment. © 2006 Nature Publishing Group.
Persistent Identifierhttp://hdl.handle.net/10722/78943
ISSN
2015 Impact Factor: 30.357
2015 SCImago Journal Rankings: 13.959
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorDe Jong, MDen_HK
dc.contributor.authorSimmons, CPen_HK
dc.contributor.authorThanh, TTen_HK
dc.contributor.authorHien, VMen_HK
dc.contributor.authorSmith, GJDen_HK
dc.contributor.authorChau, TNBen_HK
dc.contributor.authorHoang, DMen_HK
dc.contributor.authorChau, NVVen_HK
dc.contributor.authorKhanh, THen_HK
dc.contributor.authorDong, VCen_HK
dc.contributor.authorQui, PTen_HK
dc.contributor.authorCam, BVen_HK
dc.contributor.authorHa, DQen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.contributor.authorChinh, NTen_HK
dc.contributor.authorHien, TTen_HK
dc.contributor.authorFarrar, Jen_HK
dc.date.accessioned2010-09-06T07:48:41Z-
dc.date.available2010-09-06T07:48:41Z-
dc.date.issued2006en_HK
dc.identifier.citationNature Medicine, 2006, v. 12 n. 10, p. 1203-1207en_HK
dc.identifier.issn1078-8956en_HK
dc.identifier.urihttp://hdl.handle.net/10722/78943-
dc.description.abstractAvian influenza A (H5N1) viruses cause severe disease in humans, but the basis for their virulence remains unclear. In vitro and animal studies indicate that high and disseminated viral replication is important for disease pathogenesis. Laboratory experiments suggest that virus-induced cytokine dysregulation may contribute to disease severity. To assess the relevance of these findings for human disease, we performed virological and immunological studies in 18 individuals with H5N1 and 8 individuals infected with human influenza virus subtypes. Influenza H5N1 infection in humans is characterized by high pharyngeal virus loads and frequent detection of viral RNA in rectum and blood. Viral RNA in blood was present only in fatal H5N1 cases and was associated with higher pharyngeal viral loads. We observed low peripheral blood T-lymphocyte counts and high chemokine and cytokine levels in H5N1-infected individuals, particularly in those who died, and these correlated with pharyngeal viral loads. Genetic characterization of H5N1 viruses revealed mutations in the viral polymerase complex associated with mammalian adaptation and virulence. Our observations indicate that high viral load, and the resulting intense inflammatory responses, are central to influenza H5N1 pathogenesis. The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment. © 2006 Nature Publishing Group.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/nmen_HK
dc.relation.ispartofNature Medicineen_HK
dc.subject.meshAdolescenten_HK
dc.subject.meshAdulten_HK
dc.subject.meshChilden_HK
dc.subject.meshChild, Preschoolen_HK
dc.subject.meshCytokines - blood - metabolismen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshHumansen_HK
dc.subject.meshInfanten_HK
dc.subject.meshInfluenza A Virus, H5N1 Subtype - pathogenicityen_HK
dc.subject.meshInfluenza, Human - blood - mortality - virologyen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshRNA, Viral - metabolismen_HK
dc.subject.meshT-Lymphocytes - metabolismen_HK
dc.subject.meshTreatment Outcomeen_HK
dc.titleFatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemiaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1078-8956&volume=&spage=&epage=&date=2006&atitle=Fatal+outcome+of+human+influenza+A+(H5N1)+is+associated+with+high+viral+load+and+hypercytokinemia.en_HK
dc.identifier.emailSmith, GJD: gjsmith@hkucc1.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authoritySmith, GJD=rp00444en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nm1477en_HK
dc.identifier.pmid16964257-
dc.identifier.scopuseid_2-s2.0-33749511112en_HK
dc.identifier.hkuros120650en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33749511112&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume12en_HK
dc.identifier.issue10en_HK
dc.identifier.spage1203en_HK
dc.identifier.epage1207en_HK
dc.identifier.isiWOS:000241102200039-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001040866-
dc.identifier.scopusauthoridDe Jong, MD=7201366838en_HK
dc.identifier.scopusauthoridSimmons, CP=7103173872en_HK
dc.identifier.scopusauthoridThanh, TT=7004531564en_HK
dc.identifier.scopusauthoridHien, VM=10043209900en_HK
dc.identifier.scopusauthoridSmith, GJD=8344015800en_HK
dc.identifier.scopusauthoridChau, TNB=8350011500en_HK
dc.identifier.scopusauthoridHoang, DM=11840376700en_HK
dc.identifier.scopusauthoridChau, NVV=23007606000en_HK
dc.identifier.scopusauthoridKhanh, TH=10041123400en_HK
dc.identifier.scopusauthoridDong, VC=8514113300en_HK
dc.identifier.scopusauthoridQui, PT=10042125000en_HK
dc.identifier.scopusauthoridCam, BV=6507177125en_HK
dc.identifier.scopusauthoridHa, DQ=7101767746en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK
dc.identifier.scopusauthoridChinh, NT=7004370201en_HK
dc.identifier.scopusauthoridHien, TT=7005271267en_HK
dc.identifier.scopusauthoridFarrar, J=7103292979en_HK
dc.identifier.citeulike886476-

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