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

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

PloS one (2014-10-02)
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
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-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.

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α-Tri-Calcium phosphate, Reagent for transient & stable DNA transfections
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β-tri-Calcium phosphate, puriss. p.a., ≥98% β-phase basis (unsintered powder)
Sigma-Aldrich
β-tri-Calcium phosphate, puriss. p.a., ≥98% β-phase basis (sintered Powder)