title: Macrophages sustain HIV replication in vivo independently of T cells.
abstract: 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.
authors.forename: Jenna B
authors.initials: JB
authors.lastname: Honeycutt
authors.forename: Angela
authors.initials: A
authors.lastname: Wahl
authors.forename: Caroline
authors.initials: C
authors.lastname: Baker
authors.forename: Rae Ann
authors.initials: RA
authors.lastname: Spagnuolo
authors.forename: John
authors.initials: J
authors.lastname: Foster
authors.forename: Oksana
authors.initials: O
authors.lastname: Zakharova
authors.forename: Stephen
authors.initials: S
authors.lastname: Wietgrefe
authors.forename: Carolina
authors.initials: C
authors.lastname: Caro-Vegas
authors.forename: Victoria
authors.initials: V
authors.lastname: Madden
authors.forename: Garrett
authors.initials: G
authors.lastname: Sharpe
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: J Victor
authors.initials: JV
authors.lastname: Garcia
mesh_terms: D000818:Animals; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014779:Virus Replication / Q000276:immunology*