title: A Simple Mouse Model for the Study of Human Immunodeficiency Virus.
abstract: Humanized mouse models derived from immune-deficient mice have been the primary tool for studies of human infectious viruses, such as human immunodeficiency virus (HIV). However, the current protocol for constructing humanized mice requires elaborate procedures and complicated techniques, limiting the supply of such mice for viral studies. Here, we report a convenient method for constructing a simple HIV-1 mouse model. Without prior irradiation, NOD/SCID/IL2Rγ-null (NSG) mice were intraperitoneally injected with 1 × 10(7) adult human peripheral blood mononuclear cells (hu-PBMCs). Four weeks after PBMC inoculation, human CD45(+) cells, and CD3(+)CD4(+) and CD3(+)CD8(+) T cells were detected in peripheral blood, lymph nodes, spleen, and liver, whereas human CD19(+) cells were observed in lymph nodes and spleen. To examine the usefulness of hu-PBMC-inoculated NSG (hu-PBMC-NSG) mice as an HIV-1 infection model, we intravenously injected these mice with dual-tropic HIV-1DH12 and X4-tropic HIV-1NL4-3 strains. HIV-1-infected hu-PBMC-NSG mice showed significantly lower human CD4(+) T cell counts and high HIV viral loads in the peripheral blood compared with noninfected hu-PBMC-NSG mice. Following highly active antiretroviral therapy (HAART) and neutralizing antibody treatment, HIV-1 replication was significantly suppressed in HIV-1-infected hu-PBMC-NSG mice without detectable viremia or CD4(+) T cell depletion. Moreover, the numbers of human T cells were maintained in hu-PBMC-NSG mice for at least 10 weeks. Taken together, our results suggest that hu-PBMC-NSG mice may serve as a relevant HIV-1 infection and pathogenesis model that could facilitate in vivo studies of HIV-1 infection and candidate HIV-1 protective drugs.
authors.affiliation: 1 Department of Bio-industrial Technologies, College of Animal Bioscience and Technology, Konkuk University , Seoul, Korea.
authors.forename: Kang Chang
authors.initials: KC
authors.lastname: Kim
authors.affiliation: 2 Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health , Osong, Chungcheongbuk, Korea.
authors.forename: Byeong-Sun
authors.initials: BS
authors.lastname: Choi
authors.affiliation: 2 Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health , Osong, Chungcheongbuk, Korea.
authors.forename: Kyung-Chang
authors.initials: KC
authors.lastname: Kim
authors.affiliation: 1 Department of Bio-industrial Technologies, College of Animal Bioscience and Technology, Konkuk University , Seoul, Korea.
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Park
authors.affiliation: 1 Department of Bio-industrial Technologies, College of Animal Bioscience and Technology, Konkuk University , Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 3 Department of Microbiology, College of Medicine, University of Ulsan , Seoul, Korea.
authors.forename: Young Keol
authors.initials: YK
authors.lastname: Cho
authors.affiliation: 4 Division of Infectious Disease, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea , Seoul, Korea.
authors.forename: Sang Il
authors.initials: SI
authors.lastname: Kim
authors.affiliation: 2 Division of AIDS, Center for Immunology and Pathology, Korea National Institute of Health , Osong, Chungcheongbuk, Korea.
authors.forename: Sung Soon
authors.initials: SS
authors.lastname: Kim
authors.affiliation: 5 Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University , Seoul, Korea.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.affiliation: 1 Department of Bio-industrial Technologies, College of Animal Bioscience and Technology, Konkuk University , Seoul, Korea.
authors.forename: Young Bong
authors.initials: YB
authors.lastname: Kim
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D019562:Viral Load / Q000276:immunology; D014766:Viremia; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; D018941:Antigens, CD19; D017252:CD3 Complex; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit