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Article: HIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling
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TitleHIV-1 transactivator protein induction of suppressor of cytokine signaling-2 contributes to dysregulation of IFNγ signaling
 
AuthorsCheng, SM1
Li, JCB1 1
San, SL1
Lee, DCW1
Liu, L1
Chen, Z1
Lau, ASY1
 
Issue Date2009
 
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
CitationBlood, 2009, v. 113 n. 21, p. 5192-5201 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2008-10-183525
 
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.
 
ISSN0006-4971
2012 Impact Factor: 9.06
2012 SCImago Journal Rankings: 4.553
 
DOIhttp://dx.doi.org/10.1182/blood-2008-10-183525
 
ISI Accession Number IDWOS:000266404500025
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorCheng, SM
 
dc.contributor.authorLi, JCB
 
dc.contributor.authorSan, SL
 
dc.contributor.authorLee, DCW
 
dc.contributor.authorLiu, L
 
dc.contributor.authorChen, Z
 
dc.contributor.authorLau, ASY
 
dc.date.accessioned2010-05-31T03:52:09Z
 
dc.date.available2010-05-31T03:52:09Z
 
dc.date.issued2009
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationBlood, 2009, v. 113 n. 21, p. 5192-5201 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2008-10-183525
 
dc.identifier.citeulike5813803
 
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2008-10-183525
 
dc.identifier.eissn1528-0020
 
dc.identifier.epage5201
 
dc.identifier.hkuros165444
 
dc.identifier.isiWOS:000266404500025
 
dc.identifier.issn0006-4971
2012 Impact Factor: 9.06
2012 SCImago Journal Rankings: 4.553
 
dc.identifier.issue21
 
dc.identifier.openurl
 
dc.identifier.pmid19279332
 
dc.identifier.scopuseid_2-s2.0-67149099807
 
dc.identifier.spage5192
 
dc.identifier.urihttp://hdl.handle.net/10722/59534
 
dc.identifier.volume113
 
dc.languageeng
 
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBlood
 
dc.relation.referencesReferences in Scopus
 
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 signaling
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine