title: HIV-1 cellular and tissue replication patterns in infected humanized mice.
abstract: Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine; University of Nebraska Medical Center USA.
authors.forename: Mariluz
authors.initials: M
authors.lastname: Araínga
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine; University of Nebraska Medical Center USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine; University of Nebraska Medical Center USA.
authors.forename: Larisa Y
authors.initials: LY
authors.lastname: Poluektova
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine; University of Nebraska Medical Center USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, College of Medicine; University of Nebraska Medical Center USA.
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000821:virology; D001921:Brain / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003713:Dendritic Cells / Q000821:virology; D004195:Disease Models, Animal; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000821:virology; D006801:Humans; D007668:Kidney / Q000821:virology; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D008264:Macrophages / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009000:Monocytes / Q000821:virology; D013154:Spleen / Q000821:virology; D014779:Virus Replication
chemical_list: D018952:Antigens, CD34