Adenosine deaminase acting on RNA-1 (ADAR1) inhibits HIV-1 replication in human alveolar macrophages—Weiden 2014

We found A to G mutations in HIV-1 envelope sequences derived from bronchoalveolar lavage (BAL) of aerosol IFN--treated HIV-1/tuberculosis co-infected patients and ADAR1 induction in BAL cells. IFN-induced ADAR1 in MDM but not T cells. Four HIV-1-infected patients on antiretroviral treatment had HIV-1-expressing BAL cells after ADAR1 siRNA knockdown. In vitro HIV-1-infected MDM showed similar outcomes. ADAR1 overexpression in converted macrophages decreased HIV-1 viral replication but not nuclear run-on, suggesting it operates post-transcriptionally. The A to G hyper-mutation pattern in ADAR1 over-expressing cells in vitro was identical to that in the lungs of HIV-1-infected patients treated with aerosol IFN-, showing the model accurately reflected alveolar macrophages. These findings suggest that ADAR1 inhibits HIV-1 replication post-transcriptionally in HIV-1-provirus-infected macrophages. Thus, ADAR1 may affect macrophage viral latency.

Weiden, M. D., Hoshino, S., Levy, D. N., Li, Y., Kumar, R., Burke, S. A., Dawson, R., Hioe, C. E., Borkowsky, W., Rom, W. N., & Hoshino, Y. (2014). Adenosine deaminase acting on RNA-1 (ADAR1) inhibits HIV-1 replication in human alveolar macrophages. PloS one, 9(10), e108476. https://doi.org/10.1371/journal.pone.0108476