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Article: HIV-1 trans-activator protein dysregulates IFN-γ signaling and contributes to the suppression of autophagy induction

TitleHIV-1 trans-activator protein dysregulates IFN-γ signaling and contributes to the suppression of autophagy induction
Authors
Keywordsautophagy
HIV-1 tat
interferon
opportunistic infection
Issue Date2011
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.com
Citation
Aids, 2011, v. 25 n. 1, p. 15-25 How to Cite?
AbstractObjective and design: HIV-1 transactivator protein, Tat, has been identified as an activator of HIV-1 replication. It also dysregulates cytokine production and apoptosis in T-cells. Of the various cell death processes, autophagy is a self-digestion and degradation mechanism that recycles the contents of the cytosol, including macromolecules and cellular organelles, resulting in self-repair and conservation for survival. Recent reports demonstrated that autophagosomes can be activated by interferon-γ (IFN-γ) to participate in immune defence by processing foreign antigens for the recognition and killing of intracellular pathogens. As we previously showed that HIV-1 Tat perturbs IFN-γ signaling through the suppression of STAT1 phosphorylation and consequently inhibits major histocompatibility complex class-II antigen expression, we postulate that Tat plays a role in regulating autophagy. Methods: The role of STAT1 in IFN-γ-induced autophagy in primary human blood macrophages was examined using a small molecule inhibitor or siRNA specific for STAT1. The effect of HIV-1 Tat on autophagy was investigated by pretreating the macrophages with HIV-1 Tat and followed by IFN-γ stimulation. The expressions of autophagy-associated genes and their effects on engulfing mycobacteria were examined. Results: The activation of STAT1 resulted in IFN-γ-induced LC3B protein expression and autophagosome formation. As postulated, HIV-1 Tat protein suppressed IFN-γ-induced autophagy processes, including LC3B expression. Additionally, HIV-1 Tat restricted the capturing of mycobacteria by autophagosomes. Conclusion: HIV-1 Tat suppressed the induction of autophagy-associated genes and inhibited the formation of autophagosomes. Perturbation of such cellular processes by HIV-1 would impair the effective containment of invading pathogens, thereby providing a favorable environment for opportunistic microbes in HIV-infected individuals. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Persistent Identifierhttp://hdl.handle.net/10722/134854
ISSN
2015 Impact Factor: 4.407
2015 SCImago Journal Rankings: 3.112
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7685/07M
HKU7685/09M
Research Fund for the Control of Infectious Diseases (RFCID)09080512
Department of Health and Welfare Bureau, Hong Kong09080542
Funding Information:

We are grateful to our colleagues Dr Davy C.W. Lee and Ms. Anna Law (Cytokine biology group-Department of Paediatrics, The University of Hong Kong) for their helpful discussion and suggestions. This project was supported by grants to Dr A. Lau from the Hong Kong Research Grants Council (HKU7685/07M and HKU7685/09M) and Research Fund for the Control of Infectious Diseases (RFCID) Grant (09080512), and to Dr J. Li from RFCID grant (09080542), Department of Health and Welfare Bureau, Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorLi, JCBen_HK
dc.contributor.authorAu, KYen_HK
dc.contributor.authorFang, JWen_HK
dc.contributor.authorYim, HCen_HK
dc.contributor.authorChow, KHen_HK
dc.contributor.authorHo, PLen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2011-07-21T08:08:29Z-
dc.date.available2011-07-21T08:08:29Z-
dc.date.issued2011en_HK
dc.identifier.citationAids, 2011, v. 25 n. 1, p. 15-25en_HK
dc.identifier.issn0269-9370en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134854-
dc.description.abstractObjective and design: HIV-1 transactivator protein, Tat, has been identified as an activator of HIV-1 replication. It also dysregulates cytokine production and apoptosis in T-cells. Of the various cell death processes, autophagy is a self-digestion and degradation mechanism that recycles the contents of the cytosol, including macromolecules and cellular organelles, resulting in self-repair and conservation for survival. Recent reports demonstrated that autophagosomes can be activated by interferon-γ (IFN-γ) to participate in immune defence by processing foreign antigens for the recognition and killing of intracellular pathogens. As we previously showed that HIV-1 Tat perturbs IFN-γ signaling through the suppression of STAT1 phosphorylation and consequently inhibits major histocompatibility complex class-II antigen expression, we postulate that Tat plays a role in regulating autophagy. Methods: The role of STAT1 in IFN-γ-induced autophagy in primary human blood macrophages was examined using a small molecule inhibitor or siRNA specific for STAT1. The effect of HIV-1 Tat on autophagy was investigated by pretreating the macrophages with HIV-1 Tat and followed by IFN-γ stimulation. The expressions of autophagy-associated genes and their effects on engulfing mycobacteria were examined. Results: The activation of STAT1 resulted in IFN-γ-induced LC3B protein expression and autophagosome formation. As postulated, HIV-1 Tat protein suppressed IFN-γ-induced autophagy processes, including LC3B expression. Additionally, HIV-1 Tat restricted the capturing of mycobacteria by autophagosomes. Conclusion: HIV-1 Tat suppressed the induction of autophagy-associated genes and inhibited the formation of autophagosomes. Perturbation of such cellular processes by HIV-1 would impair the effective containment of invading pathogens, thereby providing a favorable environment for opportunistic microbes in HIV-infected individuals. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.en_HK
dc.languageeng-
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.AIDSonline.comen_HK
dc.relation.ispartofAIDSen_HK
dc.subjectautophagyen_HK
dc.subjectHIV-1 taten_HK
dc.subjectinterferonen_HK
dc.subjectopportunistic infectionen_HK
dc.subject.meshAutophagy - genetics - immunology-
dc.subject.meshHIV Infections - genetics - metabolism-
dc.subject.meshHIV-1 - pathogenicity-
dc.subject.meshInterferon-gamma - metabolism-
dc.subject.meshSignal Transduction - genetics - immunology-
dc.titleHIV-1 trans-activator protein dysregulates IFN-γ signaling and contributes to the suppression of autophagy inductionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0269-9370&volume=25&issue=1&spage=15&epage=25&date=2011&atitle=HIV-1+trans-activator+protein+dysregulates+IFN-γ+signaling+and+contributes+to+the+suppression+of+autophagy+induction-
dc.identifier.emailLi, JCB: jamesli@hku.hken_HK
dc.identifier.emailChow, KH: khchowb@hku.hken_HK
dc.identifier.emailHo, PL: plho@hkucc.hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLi, JCB=rp00496en_HK
dc.identifier.authorityChow, KH=rp00370en_HK
dc.identifier.authorityHo, PL=rp00406en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/QAD.0b013e328340fd61en_HK
dc.identifier.pmid21099673-
dc.identifier.scopuseid_2-s2.0-78650310661en_HK
dc.identifier.hkuros186319-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78650310661&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume25en_HK
dc.identifier.issue1en_HK
dc.identifier.spage15en_HK
dc.identifier.epage25en_HK
dc.identifier.eissn1473-5571-
dc.identifier.isiWOS:000284823900003-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectFactors affecting mycobacteria evasion of immunity: effects of HIV on cellular signaling and kinases-
dc.relation.projectEnhancement of innate immunity to the pathogen infection: anti-mycobacterial effect of IL-17-
dc.identifier.scopusauthoridLi, JCB=23103447500en_HK
dc.identifier.scopusauthoridAu, KY=36774379800en_HK
dc.identifier.scopusauthoridFang, JW=36150695100en_HK
dc.identifier.scopusauthoridYim, HC=15752404600en_HK
dc.identifier.scopusauthoridChow, KH=7202180736en_HK
dc.identifier.scopusauthoridHo, PL=7402211363en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK

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