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

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

Research output: Contribution to journalArticle

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 (US)
Article numbere108476
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2014

Fingerprint

adenosine deaminase
Adenosine Deaminase
Alveolar Macrophages
Human immunodeficiency virus 1
HIV-1
macrophages
Macrophages
RNA
Aerosols
Bronchoalveolar Lavage
aerosols
monocytes
Proviruses
Virus Latency
proviruses
T-cells
mutation
Mutation
Transcription
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Adenosine deaminase acting on RNA-1 (ADAR1) Inhibits HIV-1 replication in human alveolar macrophages. / Weiden, Michael D.; Hoshino, Satomi; Levy, David; Li, Yonghua; Kumar, Rajnish; Burke, Sean A.; Dawson, Rodney; Hioe, Catarina E.; Borkowsky, William; Rom, William N.; Hoshino, Yoshihiko.

In: PLoS One, Vol. 9, No. 10, e108476, 01.10.2014.

Research output: Contribution to journalArticle

Weiden, MD, Hoshino, S, Levy, D, Li, Y, Kumar, R, Burke, SA, Dawson, R, Hioe, CE, Borkowsky, W, Rom, WN & Hoshino, Y 2014, 'Adenosine deaminase acting on RNA-1 (ADAR1) Inhibits HIV-1 replication in human alveolar macrophages', PLoS One, vol. 9, no. 10, e108476. https://doi.org/10.1371/journal.pone.0108476
Weiden, Michael D. ; Hoshino, Satomi ; Levy, David ; Li, Yonghua ; Kumar, Rajnish ; Burke, Sean A. ; Dawson, Rodney ; Hioe, Catarina E. ; Borkowsky, William ; Rom, William N. ; Hoshino, Yoshihiko. / Adenosine deaminase acting on RNA-1 (ADAR1) Inhibits HIV-1 replication in human alveolar macrophages. In: PLoS One. 2014 ; Vol. 9, No. 10.
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