title: Modeling HIV-1 Mucosal Transmission and Prevention in Humanized Mice.
abstract: The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized.
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, 80523, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Veselinovic
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, 80523, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Charlins
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, 80523, USA. akkina@colostate.edu.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Akkina
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D002469:Cell Separation / Q000379:methods; D004195:Disease Models, Animal; D015658:HIV Infections / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016031:Liver Transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009092:Mucous Membrane / Q000473:pathology / Q000821:virology*; D013950:Thymus Gland / Q000637:transplantation
chemical_list: D019380:Anti-HIV Agents
keywords: HIV infection in humanized mice; HIV mucosal transmission; HIV pre-exposure prophylaxis; HIV vaginal and rectal transmission; HIV-1 PrEP; HIV-1 animal models; Hu-HSC and BLT mice; Modeling HIV transmission and prevention; PK-PD in HIV-1 PrEP; Preparation of humanized mice