title: Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1.
abstract: Intrarectal infection between men who have sex with men represents a predominant form of human immunodeficiency virus (HIV) transmission in developed countries. Currently there are no adequate small animal models that recapitulate intrarectal HIV transmission. Here we demonstrate that human lymphocytes generated in situ from hematopoietic stem cells reconstitute the gastrointestinal tract of humanized mice with human CD4(+) T cells rendering them susceptible to intrarectal HIV transmission. HIV infection after a single intrarectal inoculation results in systemic infection with depletion of CD4(+) T cells in gut-associated lymphoid tissue and other pathologic sequela that closely mimics those observed in HIV infected humans. This novel model provides the basis for the development and evaluation of novel approaches aimed at immune reconstitution of human gut-associated lymphoid tissue and for the development, testing, and implementation of microbicides to prevent intrarectal HIV-1 transmission.
authors: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Zhifeng
authors: Z
authors: Sun
authors: Paul W
authors: PW
authors: Denton
authors: Jacob D
authors: JD
authors: Estes
authors: Florence A
authors: FA
authors: Othieno
authors: Bangdong L
authors: BL
authors: Wei
authors: Anja K
authors: AK
authors: Wege
authors: Michael W
authors: MW
authors: Melkus
authors: Angela
authors: A
authors: Padgett-Thomas
authors: Mary
authors: M
authors: Zupancic
authors: Ashley T
authors: AT
authors: Haase
authors: J Victor
authors: JV
authors: Garcia
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012007:Rectum / Q000276:immunology / Q000293:injuries / Q000473:pathology / Q000821:virology*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D019713:Receptors, CCR5; D019718:Receptors, CXCR4