Adenosine deaminase acting on RNA-1 (ADAR1) Inhibits HIV-1 replication in human alveolar macrophages

Michael D. Weiden, Satomi Hoshino, David N. Levy, Yonghua Li, Rajnish Kumar, Sean A. Burke, Rodney Dawson, Catarina E. Hioe, William Borkowsky, William N. Rom, Yoshihiko Hoshino

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16 Scopus citations

Abstract

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-c 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.

Original languageEnglish
Article numbere108476
JournalPLoS ONE
Volume9
Issue number10
DOIs
StatePublished - 1 Oct 2014
Externally publishedYes

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