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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
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