Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1

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 lymphocy...

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Veröffentlicht in:The Journal of experimental medicine 2007-04, Vol.204 (4), p.705-714
Hauptverfasser: Sun, Zhifeng, Denton, Paul W, Estes, Jacob D, Othieno, Florence A, Wei, Bangdong L, Wege, Anja K, Melkus, Michael W, Padgett-Thomas, Angela, Zupancic, Mary, Haase, Ashley T, Garcia, J Victor
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container_issue 4
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container_title The Journal of experimental medicine
container_volume 204
creator Sun, Zhifeng
Denton, Paul W
Estes, Jacob D
Othieno, Florence A
Wei, Bangdong L
Wege, Anja K
Melkus, Michael W
Padgett-Thomas, Angela
Zupancic, Mary
Haase, Ashley T
Garcia, J Victor
description 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.
doi_str_mv 10.1084/jem.20062411
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Animals
Bone Marrow - immunology
Bone Marrow - metabolism
Brief Definitive Reports
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - metabolism
CD4-Positive T-Lymphocytes - pathology
Cell Proliferation
HIV Infections - immunology
HIV Infections - pathology
HIV Infections - transmission
HIV Infections - virology
HIV-1 - pathogenicity
HIV-1 - physiology
Humans
Liver - immunology
Liver - metabolism
Lymphoid Tissue - immunology
Lymphoid Tissue - metabolism
Mice
Phenotype
Receptors, CCR5 - metabolism
Receptors, CXCR4 - metabolism
Rectum - immunology
Rectum - injuries
Rectum - pathology
Rectum - virology
Thymus Gland - immunology
Thymus Gland - metabolism
title Intrarectal transmission, systemic infection, and CD4+ T cell depletion in humanized mice infected with HIV-1
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