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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. In order to study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11-17.5 weeks) human fetal brain or neural retina is transplanted into the anterior chamber of the eye of immunosuppressed adult rats (Epstein et al., 1992; Cvetkovich et al., 1992), and more recently in immunodeficient (SCID) mice. The human xenografts survive for many months, vascularize and form a blood-brain barrier. Immunohistochemistry with PGP 9.5 identified neuronal cell bodies and neuritic processes. Electron microscopy revealed axonal growth cones and synaptic junctions. Infection of these xenografts with cell-free HIV-1 proved difficult, however co-engraftment with HIV-1-infected human monocytes resulted in characteristic pathological changes, including the formation of syncytial giant cells, neuronal loss, and astroglial proliferation, supporting the hypothesis that these cells can mediate neurotoxicity. In other studies, xenografts of human fetal retinal tissue were readily infected with cell-free human cytomegalovirus (HCMV) strain AD169. These grafts contained cells with intracytoplasmic and intranuclear inclusions typical of HCMV infection. Productive infection within these grafts was demonstrated by the presence of immediate early, and late (capsid) HCMV antigens, by recovery of HCMV on human fibroblast cultures, and by serial passage of virus to additional retinal xenografts (DiLoreto et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human neural xenografts: progress in developing an in-vivo model to study human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. 787 92

Approximately one quarter of AIDS patients develop neurologic symptoms attributable to HIV infection within the brain. Previous studies suggest that HIV associated neurologic damage may be mediated by immune factors secreted by activated/infected CNS macrophages. We developed an in vivo system in which human embryonic brain tissue can be infected with HIV and the associated pathology monitored. In this model, dissociated human brain tissue is grown in vitro as single cell suspension in serum free medium. Fetal neural cells aggregate and form "brain microspheres" that are then transplanted into SCID mice. Pilot studies suggest that brain microspheres injected in the fat pad of SCID mice differentiate and survive for several months in vivo. Study of these grafts shows presence of functional neural cells and vascular organization suggesting a blood-brain barrier. When brain microspheres are co-cultured in vitro with HIV-infected human macrophages, virus is detected inside the human neural tissue grafts in SCID mice and measurements of viral and immune factors can be performed. To promote physiologic neuronal differentiation within the human grafts, implantation in the brain of SCID mice is being tested at the present time.
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PMID:In vivo model of HIV infection of the human brain. 787 93

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.
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PMID:SCID-Hu mouse as a model for human lung HIV-1 infection. 788 51

Human immunodeficiency virus (HIV) occurs as a number of genetic and biological variants. Of these, transmission of macrophage-tropic HIV variants appears to be favored, although most infected individuals also harbor T-cell-tropic cytopathic viruses and macrophage-tropic non-cytopathic viruses. Recent evidence regarding CD4+ T-cell depletion in vivo suggests that macrophage-tropic HIV isolates may be necessary and sufficient for the development of AIDS. This review summarizes the recent findings on macrophage-tropic viruses, and compares matched sets of experiments in HIV-infected humanized severe combined immunodeficiency (SCID) mice with a computer simulation of the lymph node microenvironment. This may help to understand why HIV infection of macrophages may have profound effects on the immune system.
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PMID:Macrophage-tropic HIV: critical for AIDS pathogenesis? 788 Mar 89

The ability to infect human peripheral blood leukocyte-reconstituted severe combined immunodeficient (hu-PBL-SCID) mice with HIV has allowed evaluation of several strategies for preventing or treating infection. In one study, hu-PBL-SCID mice derived from HIV gp160-vaccinated donors were shown to resist HIV infection, and resistance correlated best with in vitro assays of cellular immunity. We have assessed directly the importance of cellular immunity to HIV in the present experiments by the adoptive transfer of HLA-A3-restricted HIV-1 Nef-specific or HLA-B14-restricted Gag-specific CD8+ CTL clones to SCID mice bearing HLA-matched or mismatched PBL grafts. Multiple inoculations of CTL before and after HIV-1 exposure protected HLA-matched hu-PBL-SCID mice from infection, but initiation of CTL therapy on the same day as HIV infection was much less effective. However, at the high numbers of CTL required for complete protection from HIV infection, many HLA-mismatched hu-PBL-SCID mice were also protected by pre-exposure CTL transfer. Transfer of CTL with a different specificity (HTLV-1 Tax) to HLA-matched hu-PBL-SCID mice also afforded partial protection. These results suggest that HLA-restricted cytotoxicity may be less important than other nonspecific effector mechanisms for the inhibition of HIV-1 infection in vivo.
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PMID:Cloned human CD8+ cytotoxic T lymphocytes protect human peripheral blood leukocyte-severe combined immunodeficient mice from HIV-1 infection by an HLA-unrestricted mechanism. 796 48

Clinical deterioration in human immunodeficiency virus type 1 (HIV-1) disease is associated with an increased viral burden in the peripheral blood and a loss of circulating CD4+ T cells. HIV-1 isolates obtained prior to this stage of disease often have a "slow-low," non-syncytium-inducing (NSI) phenotype, whereas those obtained afterwards are often characterized as "rapid-high" and syncytium inducing (SI). Paired NSI and SI isolates from two different patients were inoculated into the human thymus implants of SCID-hu mice. The two slow-low, NSI isolates replicated to minimal levels in the grafts and did not induce thymocyte depletion. In contrast, the two SI isolates from the same patients showed high levels of viral replication and induced a marked degree of thymocyte depletion, accompanied by evidence of programmed cell death. These observations reveal a correlation between the replicative and cytopathic patterns of HIV-1 isolates in vitro and in the SCID-hu mouse in vivo and provide direct evidence that the biological phenotype of HIV-1 switch may be a causal and not a derivative correlate of HIV-1 disease progression.
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PMID:Rapid-high, syncytium-inducing isolates of human immunodeficiency virus type 1 induce cytopathicity in the human thymus of the SCID-hu mouse. 796 10

The SCID-hu mouse, a severe combined immunodeficient mouse transplanted with human hematopoietic cells, has been proposed as an experimental model for HIV-1 infection. However, like other animal models for infectious diseases, the SCID-hu mouse should provide the replication of the experimental agent without conferring any alteration during growth in the host. In this study using Southern blot hybridization, in situ hybridization and PCR analysis we demonstrate the presence of specific murine retroviral sequences in human cells recovered from the in vivo passages in SCID mice. Since the acquisition of endogenous retrovirus by human cells was demonstrated after their growth in nude mice, the data reported here extend this observation to the SCID model.
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PMID:Presence of murine retroviral sequences in human cell line transplanted in immunosuppressed SCID-mice. 796 54

Replication of the IIIB strain of human immunodeficiency virus type 1 (HIV-1IIIB) in CB.17 scid/scid mice reconstituted with human peripheral blood lymphocytes (Hu-PBL-SCID) was investigated. Hu-PBL-SCID mice could be infected, in a dose-dependent manner, when HIV-1IIIB was injected intraperitoneally. Replication-competent HIV-1 could be recovered from spleen, peripheral blood, bone marrow, thymus, lymph node, and peritoneal cavity, indicating the ability of the infection to spread to human tissue throughout the chimeric animals. HIV-1 infection was quantitated using p24 determination, end-point dilution culture, and polymerase chain reaction amplification. The level of HIV-1 replication in Hu-PBL-SCID mice was found to approximate the level reported in human infection. No HIV-1-specific immune response was generated to this infection, but nonspecific immune activation did occur, as also reported in human infection. Similarities therefore exist between HIV-1 infection of humans and Hu-PBL-SCID mice, which makes the latter an in vivo model in which to study HIV-1 replication.
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PMID:Quantitative assessment of human immunodeficiency virus type 1 replication in human xenografts of acutely infected Hu-PBL-SCID mice. 801 88

Human immunodeficiency virus (HIV) disease is typified by declining CD4+ T lymphocyte counts in the peripheral circulation, a loss which may be secondary to accelerated destruction, to suppressed differentiation, and/or to sequestration of circulating cells into tissue spaces. As it is hard to distinguish between these possibilities in human subjects, the pathogenic mechanisms associated with HIV infection are unclear. In particular, little is known about the events that occur within infected lymphoid organs in which most CD4 T lymphocytes mature and function. To obtain a better description of HIV pathogenesis in vivo, we have implanted human haematolymphoid organs into the immunodeficient SCID mouse to create the SCID-hu mouse. We have previously shown that these organ systems promote long-term multilineage human haematopoiesis and are permissive for infection with HIV. Here we report that human thymopoiesis is suppressed by HIV infection, thereby precluding regeneration of the peripheral T-cell compartment.
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PMID:HIV induces thymus depletion in vivo. 810 43

In these studies, neonatal C.B-17 severe combined immunodeficient (nSCID) mice were reconstituted with human cord blood leukocytes (hu-CBLs). The resulting hu-CBL-nSCID mice contained readily detectable human CD3+ T lymphocytes and CD20+ human B cells, and produced substantial levels of human IgM and IgG (including all subclasses). Human cells persisted in lymphoid organs and peripheral blood for at least 8 weeks, and CD4+ T cells outnumbered CD8+ T cells. Engraftment of human cells in peripheral lymphoid organs and blood was much greater than that seen in adult SCID mice grafted with adult peripheral blood leukocytes (PBLs). Hu-CBL-nSCID mice were susceptible to infection with laboratory-adapted and fresh clinical human immunodeficiency virus type 1 (HIV-1) isolates. Following infection with HIV-1, virus could be recovered by the coculture of spleen, lymph node, peritoneal cavity, liver, and plasma samples from hu-CBL-nSCID mice with fresh human peripheral blood mononuclear cells, and proviral copies were detectable following amplification using the polymerase chain reaction (PCR). HIV p24 core antigen levels in hu-CBL-nSCID mouse plasma were consistent with ongoing viral replication and high viral burdens. Rapid CD4+ T cell depletion occurred following infection with laboratory isolates of HIV-1 or a syncytium-inducing clinical isolate, but a non-syncytium-inducing clinical isolate caused expansion of CD8+ T cells, leading to an inversion of the CD4:CD8 ratio with only a transient decrease in CD4+ T cells. These results suggest that the hu-CBL-nSCID mouse system has unique features that mimic certain aspects of pediatric HIV infection, and distinguish it from other animal models of HIV infection, including the related hu-PBL-SCID model.
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PMID:Human immunodeficiency virus type 1 infection of neonatal severe combined immunodeficient mice xenografted with human cord blood cells. 819 67


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