PATHOGENESIS OF HIV INFECTION

Project: Research project

Project Details

Description

After exposure of an individual to an inoculum of HIV-1, and infectious
cycle is initiated that leads to systemic dissemination of HIV-1 and HIV-
1-infected individuals between the very active HIV-1 infection observed
in lymph nodes and the low degree of HIV-1 infection seen in peripheral
blood. A s consequence of this dichotomy, examining the peripheral blood
of HIV-1 infected individuals will not indicate the effects of
therapeutic interventions on the high degree of covert HIV-1 replication
occurring in the lymphoid tissues. We have recently described a modified
SCID-hu mouse model for disseminated HIV-1 infection consisting of human
fetal thymus and liver implanted in SCID mice. Significant numbers of
human T cells were detected in the peripheral blood, spleens and lymph
nodes of these mice and disseminated HIV infection was observed after
either intraimplant injection or intraperitoneal inoculation of HIV-1
into these SCID-hu mice. In addition to this model for in vivo HIV-1-
infection of human T cells, we have also developed a model, BM-SCID-hu
mice, that can be used to study the in vivo HIV-1-infection of human
monocytes and BM-SCID-hu mice, that can be used to study the in vivo HIV-
1 infection of human monocytes and B cells. After transplantation of
irradiated SCID mice with cultured human fetal bone marrow cells, the
bone marrow of these BM-SCID-hu mice become significantly engrafted with
human precursor cells independent of the administration of extraneous
human cytokines and the peripheral lymphoid compartment of these mice are
reconstituted with human B cells and monocytes. By transplanting SCID
mice implanted with human fetal thymus and liver with human fetal bone
marrow, we have generated mice wherein human hematopoiesis is occurring
in the mouse bone marrow and the peripheral lymphoid compartment is
populated with human T cells, B cells and monocytes. Therefore, we
propose to utilize these animal models to study the pathogenesis of acute
and chronic HIV-1 infection in vivo and to investigate the effects of
various anti-HIV interventions on disseminated HIV-infection present in
their peripheral blood, lymphoid compartment, thymus and bone marrow of
these mice.
StatusFinished
Effective start/end date7/1/946/30/95

Funding

  • National Institute of Allergy and Infectious Diseases

ASJC

  • Microbiology (medical)
  • Infectious Diseases
  • Molecular Medicine
  • Virology
  • Immunology

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