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

Murine models with type C murine leukemia viruses have been used to develop major new prophylactic and therapeutic strategies in vaccination, drug therapy of acute virus exposure and chronic viremia, combination therapy, prevention of maternal transmission, and therapy targeted to the central nervous system. Transgenic mice expressing either the whole human immunodeficiency virus type 1 (HIV-1) provirus or subgenomic sequences allow the in vivo analysis of selected HIV-1 functions. The full replicative cycle of HIV-1 can be studied in human/mouse chimerae which were created by transplanting human hematolymphoid cells into SCID mice. The chimeric SCID mouse models have been used successfully to evaluate anti-HIV-1 drugs. The role of the various murine retrovirus systems in the development of anti-HIV-1 and anti-AIDS therapies is summarized.
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PMID:Development of antiviral treatment strategies in murine models. 132 85

Epstein-Barr virus (EBV) infection is associated with Burkitt's lymphoma (BL) in normal individuals and immunoblastic B cell lymphomas in immunosuppressed or HIV-infected individuals. SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors also may develop spontaneous B cell lymphomas which histologically and phenotypically resemble post-transplant tumors, and are distinct from BL. These tumors always contain EBV DNA. We have noted three different reproducible outcomes depending upon the EBV-seropositive donor used for generation of hu-PBL-SCID mice: (i) no tumors appear; (ii) tumors appear in a fraction of hu-PBL-SCID mice with a 10-20 wk. latent period; or (iii) tumors appear in all hu-PBL-SCID mice within 6-10 wk. Southern blot analysis of late versus early tumors using a probe specific for the EBV terminal repeat sequences (BamNJ), which allows distinction between circular latent and linear replicating genomes, shows that late tumors do not involve active EBV replication but that early tumors do show replicating genomes. In addition, EBV genomes were monoclonal in late tumors but polyclonal in early tumors. These data suggest two mechanisms for EBV lymphomagenesis, slow outgrowth of rare latently-infected B cells, and more rapid transformation of uninfected bystander B cells by replicating virus. The latter process may be highly amenable to therapy in patients at risk for EBV-related lymphomas. In addition, prospective screening of EBV-seropositive transplant recipients in the hu-PBL-SCID model may predict the risk of post-transplant lymphoma development.
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PMID:EBV-induced human B cell lymphomas in hu-PBL-SCID mice. 132 70

Primate and non-primate species have been used to study the pathobiology of the simian immunodeficiency virus (SIV) and of the human immunodeficiency virus type 1 (HIV-1), respectively, and to develop new therapeutic regimes. Transgenic mice which express either the entire HIV-1 provirus or subgenomic fragments have been used to analyze viral gene products in vivo and may serve as models for the development of agents targeted to select viral functions. Chimeric mice which were created by transplanting human hematolymphoid cells into mice suffering from congenital severe combined immunodeficiency (scid/scid or so called SCID mice), can be infected with HIV-1 and allow one to study the entire HIV-1 replicative cycle. Type C murine leukemia virus models have been used to develop new prophylactic and therapeutic strategies but their use is restricted to the evaluation of select antiviral drug inhibition, targeted to retroviral genes common to both Lentivirinae and Oncovirinae. The role of various animal model systems in the development of anti-HIV-1 and anti-AIDS therapies is summarized.
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PMID:Animal models for anti-AIDS therapy. 144 26

For the sake of clarity and in agreement with the World Health Organization immunodeficiency classification, it is important to distinguish the congenital, inherited malformative lesions called generically 'thymic dysplasia' from the secondary, acquired changes, designated under the broad term of 'severe thymic atrophy'. Thymic dysplasia represents the archetype of thymic changes in cellular immunodeficiency, since there is no example of a thymic dysplasia associated with a normal T-cell function. Thymic dysplasia is observed in several inherited diseases, the most frequent of them being severe combined immunodeficiency. More than the depletion of lymphoid cells, the lack of differentiation of the thymic epithelium, responsible for the absence of Hassal's corpuscles, is the main and constant feature of this condition. Thymic dysplasia underscores the crucial role of the thymic epithelium in the normal differentiation of the T-cell population. Severe thymic atrophy is secondary to various causes, including prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction and, chiefly today, chronic viral infection, especially with HIV-1. The morphological changes are similar and are characterized by a partial lymphoid depletion, involving mainly the CD1+ population, necrosis and calcification of epithelial cells, the frequent presence of plasma cells and, more significantly, fibrohyaline changes of the basement membrane of the vessels and thymic epithelium. The severity of the atrophic changes and the immunodeficiency-related manifestations depend on the duration of the aetiological factors and, more significantly, with their early occurrence, within the first months of life. The mechanisms underlying thymic atrophy are poorly understood. A primary impairment of lymphoid cells seems at present to be the most likely hypothesis.
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PMID:Thymic pathology in primary and secondary immunodeficiencies. 146 48

Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection.
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PMID:Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication. 171 88

Work in the SCID-hu system has progressed significantly over the past 3-4 years. Reliable SCID-hu constructs can now be created for the evaluation of long-term multilineage human hematopoiesis, human immune function, and HIV infection of human hematolymphoid organs in vivo. Given these constructs, a variety of therapeutically important modalities can now be discovered and developed with a relevant in vivo model, prior to the time that they are moved into the clinic. With further progress in this and other preclinical models, useful therapies for important human disease states will hopefully be forthcoming at an even faster pace.
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PMID:Preclinical evaluation of human hematolymphoid function in the SCID-hu mouse. 180 80

Adenosine deaminase is an enzyme that actively participates in the metabolism of the adenine nucleotides. It catalyzes the irreversible hydrolytic deamination of deoxyadenosine and adenosine with the production of deoxyinosine and inosine respectively and of ammonia. This enzyme thus plays an important role in lympho-monocyte maturation and activation. The increase in its activity in different biological fluids (pleural, pericardial, peritoneal, intra-articular and cerebrospinal fluids) has been used as a rapid diagnostic test in tuberculosis infection. In human immunodeficiency virus infection, it was verified that enzymatic activity progressively increases in serum and blood cells, accompanying the natural evolution of the disease. The physiopathological mechanism has not been definitely established but the CD4+ lymphocytes and macrophages are pointed to as being accountable for the enzyme's increase in activity. For this reason, adenosine deaminase could be a marker of the cellular immune response. The study of adenosine deaminase activity in blood cells elucidated the diagnosis of severe combined immunodeficiency (due to a congenital lack of the enzyme) in 30 to 50% of the cases. One type of congenital hemolytic anemia is due to an exaggerated enzymatic activity in red blood cells.
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PMID:[Adenosine deaminase. A pluridisciplinary enzyme]. 180 98

The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; greater than 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV.
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PMID:Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouse. 190 43

The SCID-hu mouse is a heterochimeric small animal model designed to support hematopoietic differentiation and function in vivo. Multiple organs of the human hematolymphoid system have been successfully engrafted into the immunodeficient C.B-17 scid scid mouse, including fetal liver, thymus, lymph node, and skin. Co-implantation of human fetal liver and human fetal thymus results in long-term, multilineage human hematopoiesis in vivo. Mature human lymphocytes within the SCID-hu mouse are phenotypically and functionally normal. HIV infection of the SCID-hu mouse reflects a tropism similar to that found in humans: only human organs with CD4+ cells are infected. Viral replication can thereafter be monitored with assays that are safe, reproducible, and quantitative. Given this small animal model, it is now possible to study systematically the infective process of HIV and to address questions about the efficacy of novel antiviral compounds or vaccines in vivo.
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PMID:The SCID-hu mouse: a small animal model for HIV infection and pathogenesis. 191 Jun 84

Though the development of human-to-mouse xenotransplant models is in its infancy, astonishing progress has been made in a short period of time. Two experimental applications have been developed: short-term transfer of human lymphocytes to generate models for autoimmunity and infectious diseases, and long-term engraftment of tissues with self-renewal potential. Human PBL-SCID mice have been used by multiple laboratories to study normal and autoimmune antibody responses, and have been shown to be readily infectable with HIV-1. SCID mice grafted with fetal tissue have been developed for studies of HIV-1 infection and its therapy as well as for studies of human hematopoietic cell differentiation. Human tumors appear to grow better in SCID mice than in nude mice, and hu-PBL-SCID mice can develop EBV-related B cell lymphoproliferative disease that resembles the immunoblastic lymphomas appearing in immunosuppressed transplant recipients. There is some evidence of mouse NK cells responding to the human xenograft, and of human T and B cells responding to mouse xenoantigens in these models, but these responses are not generally strong enough to have a major impact on human immune function. The use of these surrogate human models is expected to have a major impact on the understanding and treatment of human disease.
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PMID:Adoptive transfer of human lymphoid cells to severely immunodeficient mice: models for normal human immune function, autoimmunity, lymphomagenesis, and AIDS. 195 Jul 98


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