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 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.
Sun
Zhifeng
Z
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Denton
Paul W
PW
Estes
Jacob D
JD
Othieno
Florence A
FA
Wei
Bangdong L
BL
Wege
Anja K
AK
Melkus
Michael W
MW
Padgett-Thomas
Angela
A
Zupancic
Mary
M
Haase
Ashley T
AT
Garcia
J Victor
JV
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
C514936:CXCR4 protein, mouse; D019713:Receptors, CCR5; D019718:Receptors, CXCR4