Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages

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dc.contributor.authorWeiden, Michael Den_ZA
dc.contributor.authorHoshino, Satomien_ZA
dc.contributor.authorLevy, David Nen_ZA
dc.contributor.authorLi, Yonghuaen_ZA
dc.contributor.authorKumar, Rajnishen_ZA
dc.contributor.authorBurke, Sean Aen_ZA
dc.contributor.authorDawson, Rodneyen_ZA
dc.contributor.authorHioe, Catarina Een_ZA
dc.contributor.authorBorkowsky, Williamen_ZA
dc.contributor.authorRom, William Nen_ZA
dc.contributor.authorHoshino, Yoshihikoen_ZA
dc.date.accessioned2016-01-11T06:56:07Z
dc.date.available2016-01-11T06:56:07Z
dc.date.issued2014en_ZA
dc.description.abstractWhile exploring the effects of aerosol IFN-γ treatment in HIV-1/tuberculosis co-infected patients, we observed A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL) of aerosol IFN-γ-treated patients and induction of adenosine deaminase acting on RNA 1 (ADAR1) in the BAL cells. IFN-γ induced ADAR1 expression in monocyte-derived macrophages (MDM) but not T cells. ADAR1 siRNA knockdown induced HIV-1 expression in BAL cells of four HIV-1 infected patients on antiretroviral therapy. Similar results were obtained in MDM that were HIV-1 infected in vitro . Over-expression of ADAR1 in transformed macrophages inhibited HIV-1 viral replication but not viral transcription measured by nuclear run-on, suggesting that ADAR1 acts post-transcriptionally. The A to G hyper-mutation pattern observed in ADAR1 over-expressing cells in vitro was similar to that found in the lungs of HIV-1 infected patients treated with aerosol IFN-γ suggesting the model accurately represented alveolar macrophages. Together, these results indicate that ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus. ADAR1 may therefore contribute to viral latency in macrophages.en_ZA
dc.identifier.apacitationWeiden, M. D., Hoshino, S., Levy, D. N., Li, Y., Kumar, R., Burke, S. A., ... Hoshino, Y. (2014). Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages. <i>PLoS One</i>, http://hdl.handle.net/11427/16302en_ZA
dc.identifier.chicagocitationWeiden, Michael D, Satomi Hoshino, David N Levy, Yonghua Li, Rajnish Kumar, Sean A Burke, Rodney Dawson, et al "Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16302en_ZA
dc.identifier.citationWeiden, M. D., Hoshino, S., Levy, D. N., Li, Y., Kumar, R., Burke, S. A., ... & Hoshino, Y. (2013). Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages. PloS one, 9(10), e108476. doi:10.1371/journal.pone.0108476en_ZA
dc.identifier.ris TY - Journal Article AU - Weiden, Michael D AU - Hoshino, Satomi AU - Levy, David N AU - Li, Yonghua AU - Kumar, Rajnish AU - Burke, Sean A AU - Dawson, Rodney AU - Hioe, Catarina E AU - Borkowsky, William AU - Rom, William N AU - Hoshino, Yoshihiko AB - While exploring the effects of aerosol IFN-γ treatment in HIV-1/tuberculosis co-infected patients, we observed A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL) of aerosol IFN-γ-treated patients and induction of adenosine deaminase acting on RNA 1 (ADAR1) in the BAL cells. IFN-γ induced ADAR1 expression in monocyte-derived macrophages (MDM) but not T cells. ADAR1 siRNA knockdown induced HIV-1 expression in BAL cells of four HIV-1 infected patients on antiretroviral therapy. Similar results were obtained in MDM that were HIV-1 infected in vitro . Over-expression of ADAR1 in transformed macrophages inhibited HIV-1 viral replication but not viral transcription measured by nuclear run-on, suggesting that ADAR1 acts post-transcriptionally. The A to G hyper-mutation pattern observed in ADAR1 over-expressing cells in vitro was similar to that found in the lungs of HIV-1 infected patients treated with aerosol IFN-γ suggesting the model accurately represented alveolar macrophages. Together, these results indicate that ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus. ADAR1 may therefore contribute to viral latency in macrophages. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0108476 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages TI - Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages UR - http://hdl.handle.net/11427/16302 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16302
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0108476
dc.identifier.vancouvercitationWeiden MD, Hoshino S, Levy DN, Li Y, Kumar R, Burke SA, et al. Adenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophages. PLoS One. 2014; http://hdl.handle.net/11427/16302.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Weiden et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherSmall interfering RNAsen_ZA
dc.subject.otherViral replicationen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherAntiretroviral therapyen_ZA
dc.subject.otherAerosolsen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherTuberculosisen_ZA
dc.titleAdenosine Deaminase Acting on RNA-1 (ADAR1) Inhibits HIV-1 Replication in Human Alveolar Macrophagesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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