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Article: HIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling

TitleHIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling
Authors
Issue Date2009
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2009, v. 113 n. 21, p. 5192-5201 How to Cite?
AbstractHIV infection remains a worldwide threat. HIV-1 transactivator protein Tat is one of the retroviral proteins identified as a key immunomodulator in AIDS pathogenesis. Although the primary function of Tat is to regulate HIV-1 replication in the infected cell, it also dysregulates cytokine production resulting in perturbation of the host immune response and enhancement of the retrovirus survival. Because interferon-γ (IFNγ) is a pleiotropic cytokine with potent antiviral and immunoregulatory effects, we investigated whether Tat interferes with the IFNγ signal transduction in primary monocytes. We demonstrated that Tat impaired the IFNγ-receptor signaling pathway at the level of STAT1 activation, possibly via Tat-dependent induction of suppressor of cytokine signaling-2 (SOCS-2) activity. We delineated the inhibitory role of SOCS-2 in IFNγ signaling pathway by overexpression of exogenous SOCS-2 in HEK293 cell. The results showed that SOCS-2 suppressed the IFNγ-activated STAT1 phosphorylation and consequent IFNγ-regulated transcription of specific genes. To confirm the role of SOCS2 in the Tat-induced process, we demonstrated that SOCS-2 siRNA in human blood monocytes abrogated the Tat-dependent inhibition of IFNγ signaling. Our data suggested a possible mechanism implicating the role of SOCS-2 in mediating HIV-1-induced immune evasion and dysregulation of IFNγ signaling in primary human monocytes. © 2009 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/59534
ISSN
2023 Impact Factor: 21.0
2023 SCImago Journal Rankings: 5.272
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheng, SMen_HK
dc.contributor.authorLi, JCBen_HK
dc.contributor.authorSan, SLen_HK
dc.contributor.authorLee, DCWen_HK
dc.contributor.authorLiu, Len_HK
dc.contributor.authorChen, Zen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-05-31T03:52:09Z-
dc.date.available2010-05-31T03:52:09Z-
dc.date.issued2009en_HK
dc.identifier.citationBlood, 2009, v. 113 n. 21, p. 5192-5201en_HK
dc.identifier.issn0006-4971en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59534-
dc.description.abstractHIV infection remains a worldwide threat. HIV-1 transactivator protein Tat is one of the retroviral proteins identified as a key immunomodulator in AIDS pathogenesis. Although the primary function of Tat is to regulate HIV-1 replication in the infected cell, it also dysregulates cytokine production resulting in perturbation of the host immune response and enhancement of the retrovirus survival. Because interferon-γ (IFNγ) is a pleiotropic cytokine with potent antiviral and immunoregulatory effects, we investigated whether Tat interferes with the IFNγ signal transduction in primary monocytes. We demonstrated that Tat impaired the IFNγ-receptor signaling pathway at the level of STAT1 activation, possibly via Tat-dependent induction of suppressor of cytokine signaling-2 (SOCS-2) activity. We delineated the inhibitory role of SOCS-2 in IFNγ signaling pathway by overexpression of exogenous SOCS-2 in HEK293 cell. The results showed that SOCS-2 suppressed the IFNγ-activated STAT1 phosphorylation and consequent IFNγ-regulated transcription of specific genes. To confirm the role of SOCS2 in the Tat-induced process, we demonstrated that SOCS-2 siRNA in human blood monocytes abrogated the Tat-dependent inhibition of IFNγ signaling. Our data suggested a possible mechanism implicating the role of SOCS-2 in mediating HIV-1-induced immune evasion and dysregulation of IFNγ signaling in primary human monocytes. © 2009 by The American Society of Hematology.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_HK
dc.relation.ispartofBlooden_HK
dc.rightsThis research was originally published in The Hematologist: ASH News and Reports. Author(s). Title. The Hematologist: ASH News and Reports. Year;Vol,Issue:pp-pp. © the American Society of Hematology.-
dc.subject.meshHIV-1 - pathogenicity-
dc.subject.meshInterferon-gamma - metabolism-
dc.subject.meshMonocytes - virology-
dc.subject.meshSuppressor of Cytokine Signaling Proteins - genetics-
dc.subject.meshTranscriptional Activation-
dc.titleHIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signalingen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-4971&volume=113 &issue=21&spage=5192&epage=5201&date=2009&atitle=HIV-1+transactivator+protein+induction+of+suppressor+of+cytokine+signaling-2+contributes+to+dysregulation+of+IFN+(gamma)+signalingen_HK
dc.identifier.emailLi, JCB: jamesli@hku.hken_HK
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hken_HK
dc.identifier.emailChen, Z: zchenai@hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLi, JCB=rp00496en_HK
dc.identifier.authorityLiu, L=rp00268en_HK
dc.identifier.authorityChen, Z=rp00243en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1182/blood-2008-10-183525en_HK
dc.identifier.pmid19279332en_HK
dc.identifier.scopuseid_2-s2.0-67149099807en_HK
dc.identifier.hkuros165444en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67149099807&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume113en_HK
dc.identifier.issue21en_HK
dc.identifier.spage5192en_HK
dc.identifier.epage5201en_HK
dc.identifier.eissn1528-0020-
dc.identifier.isiWOS:000266404500025-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheng, SM=19638747100en_HK
dc.identifier.scopusauthoridLi, JCB=23103447500en_HK
dc.identifier.scopusauthoridSan, SL=36905562500en_HK
dc.identifier.scopusauthoridLee, DCW=15751156000en_HK
dc.identifier.scopusauthoridLiu, L=35784425200en_HK
dc.identifier.scopusauthoridChen, Z=35271180800en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.citeulike5813803-
dc.identifier.issnl0006-4971-

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