TY - JOUR AU - Honeycutt, Jenna B. AU - Wahl, Angela AU - Baker, Caroline AU - Spagnuolo, Rae Ann AU - Foster, John AU - Zakharova, Oksana AU - Wietgrefe, Stephen AU - Caro-Vegas, Carolina AU - Madden, Victoria AU - Sharpe, Garrett AU - Haase, Ashley T. AU - Eron, Joseph J. AU - Garcia, J. Victor T1 - Macrophages sustain HIV replication in vivo independently of T cells PY - 2016/04/01/ AB - Macrophages have long been considered to contribute to HIV infection of the CNS; however, a recent study has contradicted this early work and suggests that myeloid cells are not an in vivo source of virus production. Here, we addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. We were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. To determine whether tissue macrophages are productively infected, we used 3 different but complementary humanized mouse models. Two of these models (bone marrow/liver/thymus [BLT] mice and T cell–only mice [ToM]) have been previously described, and the third model was generated by reconstituting immunodeficient mice with human CD34+ hematopoietic stem cells that were devoid of human T cells (myeloid-only mice [MoM]) to specifically evaluate HIV replication in this population. Using MoM, we demonstrated that macrophages can sustain HIV replication in the absence of T cells; HIV-infected macrophages are distributed in various tissues including the brain; replication-competent virus can be rescued ex vivo from infected macrophages; and infected macrophages can establish de novo infection. Together, these results demonstrate that macrophages represent a genuine target for HIV infection in vivo that can sustain and transmit infection. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI84456 VL - 126 IS - 4 UR - https://doi.org/10.1172/JCI84456 SP - 1353 EP - 1366 PB - The American Society for Clinical Investigation ER -