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
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
DOIhttp://dx.doi.org/10.1182/blood-2008-10-183525
ISI Accession Number IDWOS:000266404500025
ReferencesReferences in Scopus
DC Field
Value
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.epage5201
dc.identifier.hkuros165444
dc.identifier.isiWOS:000266404500025
dc.identifier.issn0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
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
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine