Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We constructed three simian-human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity against challenge infection with gene-intact SHIV in rhesus macaques. Inoculation of SHIV-dn lacking nef and SHIV-drn lacking nef and vpr induced transient viremia, while that of SHIV-dxrn lacking nef, vpr, and vpx induced no viremia. The SHIVs with fewer deletions were more effective in inducing neutralizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene-intact SHIV-NM-3rN, all the SHIV-dn-vaccinated macaques and two of the four SHIV-drn-vaccinated macaques showed complete resistance. The other two SHIV-drn-vaccinated macaques and all SHIV-dxrn-vaccinated macaques did not show complete resistance, but they did show suppression of replication of the challenge virus. These results suggested that as more genes were deleted, protective immunity was decreased.
J Med Primatol
PMID:Protective immunity of gene-deleted SHIVs having an HIV-1 Env against challenge infection with a gene-intact SHIV. 1059 91

We have previously demonstrated that peptide immunization restimulates the memory CD4 T-cell response, but fails to induce cytotoxic T lymphocyte (CTL) in cynomolgus macaques. To examine the nature of protective immunity to simian immunodeficiency virus (SIV) in this study, freshly isolated peripheral blood mononuclear cells (PBMC) from four infected juvenile cynomolgus macaques and from three uninfected control macaques were assessed for CTL activity monthly for 9 consecutive months, beginning 1 month after detection of infection. Target cells consisted of major histocompatibility (MHC) haploidentical parental PBMC which were stimulated with mitogen and then pulsed with heat-killed SIVcyn. CTL activity was demonstrated in PBMCs from all four infected animals. The effector cells are T cells which mediate cytotoxicity against SIVcyn-pulsed target cells in an MHC-restricted manner. Furthermore, the cytotoxicity is virus specific and predominantly, if not exclusively, mediated by CD8+ T cells; it is also MHC class I restricted. Incubation of target cells with pepstatin A during antigen pulsing prior to the cytotoxic assay inhibited target cell generation, suggesting that viral antigens are processed via an endocytic pathway.
J Med Primatol 1999 Dec
PMID:Detection of simian immunodeficiency virus (SIV)-specific T-cell-mediated cytotoxicity in the peripheral blood from infected cynomolgus monkeys. 1875 49

Eight cases of extranodal non-Hodgkin's lymphoma in simian immunodeficiency virus (SIV)-infected rhesus macaques, aged 4-9 years, were phenotypically and immunologically characterized, using the updated Kiel classification, in order to determine both the differences and the similarities between these types of lymphoma in immunodeficient rhesus macaques (Macaca mulatta) and man. The high-grade malignant tumors were of B-cell origin, with a predilection for extranodal growth in viscera and periorbital tissues. Immunophenotypical characterization showed that the monkey lymphomas were similar in many aspects to human immunodeficiency virus-associated lymphomas. The number of Ki67 positive cells varied from case to case and ranged from 50 to 90%. A serological screening for the simian equivalent of the Epstein-Barr virus (sEBV) by immunofluorescence assay revealed a prevalence of 92% of the sEBV antibodies in our cohort. The presence of Ebstein-Barr virus nuclear antigen (EBNA-2) could be demonstrated by immunohistochemistry in four out of eight cases. In situ hybridization revealed the presence of small EBV-encoded RNAs (EBER-1, EBER-2) in six of the eight cases. Further studies should define the precise role of herpesvirus infection for lymphomagenesis in SIV-induced immunodeficiency.
J Med Primatol 1999 Dec
PMID:Morphologic and immunophenotypic characteristics of malignant lymphomas in SIV-infected rhesus macaques. 1073 4

The potential therapeutic utility of thalidomide (Thd), an effective inhibitor of tumor necrosis factor (TNF)-alpha in vitro, was investigated in cynomolgus monkeys (Macaca fascicularis) at 10 months after infection with simian immunodeficiency virus (SIV). Thd-treated macaques (n = 8) received an oral dose (10 mg) daily for 7 days, followed by a wash-out period of 5 weeks. A 2nd cycle of treatment was performed on the same animals at higher doses (20 mg Thd/day) for 14 days. The control monkeys (n = 7) received a placebo for the same period of time. In the present study, we show that Thd, in addition to inhibiting TNF-alpha production after in vitro mitogen stimulation of peripheral blood mononuclear cells (PBMCs), was able to restore the proliferative responses to SIV peptides in monkeys that were infected with SIV. Interestingly, we found that such effects are associated with an increased expression of CD28 cell surface receptors on CD4+ T-cells paralleled by a decrease on CD8+ T-cells. At the same time, significant reduction in either cell-associated viral load or plasma viral RNA was not observed among the SIV-infected monkeys during the two treatment cycles, when compared with the placebo group.
J Med Primatol 2000 Feb
PMID:Study of immunological and virological parameters during thalidomide treatment of SIV-infected cynomolgus monkeys. 1087 Jun 69

Comparative studies were performed to determine the neuropathogenesis of infection in macaques with simian human immunodeficiency virus (SHIV)89.6P and SHIV(KU). Both viruses utilize the CD4 receptor and CXCR4 co-receptor. However, in addition, SHIV89.6P uses the CCR5 co-receptor. Both agents are dual tropic for CD4+ T cells and blood-derived macrophages of rhesus macaques. Following inoculation into macaques, both caused rapid elimination of CD4+ T cells but they varied greatly in mechanisms of neuropathogenesis. Two animals infected with SHIV89.6P developed typical lentiviral encephalitis in which multinucleated giant cell formation, nodular accumulations of microglial cells, activated macrophages and astrocytes, and perivascular accumulations of mononuclear cells were present in the brain. Many of the macrophages in these lesions contained viral RNA. Three macaques infected with SHIV(KU) and killed on days 6, 11 and 18, respectively, developed a slowly progressive infection in the CNS but macrophages were not productively infected and there were no pathological changes in the brain. Two other animals infected with this virus and killed several months later showed minimal infection in the brain even though one of the two developed encephalitis of unknown etiology. The basic difference in the mechanisms of neuropathogenesis by the two viruses may be related to co-receptor usage. SHIV89.6P, in utilizing the CCR5 co-receptor, caused neuropathogenic effects that are similar to other neurovirulent primate lentiviruses.
J Med Primatol 2000 Aug
PMID:Neuropathogenesis of chimeric simian human immunodeficiency virus infection in rhesus macaques. 1108 71

Non-human primate models for acquired immunodeficiency syndrome (AIDS) are important for studies of prevention and intervention strategies. Ideally, such models would make use of human immunodeficiency virus type 1 (HIV-1) and animals that are readily available for research. HIV-1 was obtained from an infected macaque, and passaged sequentially in three groups of two Macaca nemestrina neonates each. Evidence for enhanced viral replication was first found in one of the group 2 animals, and in both group 3 animals. Observations that underlie this conclusion are sustained viral recovery from peripheral blood mononuclear cells (PBMCs), increased and accelerated production of antiviral antibodies, and the ability to detect plasma viral ribonucleic acid (RNA) months after infection. There was no evidence of CD4 depletion in any of the animals during the follow-up period. These data suggest that a useful non-human primate model for AIDS can be attained in pigtailed macaques (M. nemestrina).
J Med Primatol 2000 Aug
PMID:Enhanced replication of HIV-1 in vivo in pigtailed macaques (Macaca nemestrina). 1108 72

With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) infection. We report here that an isolate of HIV type 2, EHO, readily established persistent infection in 100% of Macaca nemestrina in three consecutive transmission studies. Of the eight infected animals, five showed persistently high virus load and six developed AIDS-like diseases or CD4+ cell depletion within 4 years of infection. The pathology and clinical signs closely parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4+ cell depletion, and opportunistic infections. A cell-free virus stock was established from the lymph nodes of an animal that developed AIDS-like diseases. This virus, HIV-2/287, was highly pathogenic in M. nemestrina, causing CD4+ cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows greatly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that causes rapid and reproducible CD4 cell depletion in macaques could facilitate the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.
J Med Primatol 2000 Aug
PMID:Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina. 1108 73

Primary infection of rhesus macaques with pathogenic strains of simian immunodeficiency virus (SIV) leads to rapid and dynamic changes in both viral load and T cell counts in the peripheral blood. We have performed a sequential analysis of peripheral blood CD4 and CD8 T cells in five macaques during the 8 weeks following SIVmac251 infection. We observed a transient lymphopenia of both CD4 and CD8 T cells during the first 2 weeks, followed by a rebound. The primary phase of infection was associated with changes in the T cells expressing CD25, CD69, or HLA-DR and with a priming of the peripheral blood CD4 and CD8 T cells for a process of apoptosis in vitro that was enhanced by CD95 (Fas) ligation, and was detected in two macaques as early as 7 days after infection. Despite the small numbers of animals studied, the importance of the early transient CD4 and CD8 T lymphopenia was positively correlated with the viral load. No correlation was found, however, between the level of activation markers expressed or of priming for apoptosis in peripheral blood T cells and the viral load. Our findings suggest the possibility that the early activation and priming for apoptosis of CD4 and CD8 T cells may involve indirect, host-related, mechanisms, or alternatively, that the T cells that remain in the peripheral blood during primary infection do not adequately reflect the viral-mediated changes in T cell activation and death that may occur in the lymphoid organs throughout the body.
J Med Primatol 2000 Aug
PMID:Early changes in peripheral blood T cells during primary infection of rhesus macaques with a pathogenic SIV. 1108 74

After experimental infection with simian immunodeficiency virus (SIV), intestinal endoscopy proved to be an easily tolerated, minimal invasive procedure to obtain biopsies from the gastrointestinal tract of rhesus macaques during all stages of disease. As the GI tract is affected by many opportunistic infections and immunological impairment after SIV/human immunodeficiency virus (HIV) infection, knowledge on the proviral load is an important parameter for a better understanding of disease pathogenesis. In this paper, we describe the set-up and evaluation of a quantitative competitive polymerase chain reaction (PCR) and the quantification of SIV intestinal proviral load in a long-term follow-up study of eight rhesus monkeys (Macaca mulatta) after two different routes of virus inoculation. A SIV-specific signal could be detected as early as day 3 after infection. Of 143 biopsies from the follow-up study, 85.3% showed a positive PCR. DNA copy numbers ranged from 300 to 15,000 molecules per 100,000 cells. No significant influence of the inoculation route could be shown on either proviral load or survival time, but higher SIV proviral load was associated with a more rapid progression to disease. Therefore, the amount of proviral load in intestinal biopsies may be an important prognostic value for the further course of the disease.
J Med Primatol 2000 Aug
PMID:Long-term follow-up study on SIV intestinal proviral load in rhesus macaques. 1108 75

The dynamics of T cells expressing the gammadelta T-cell receptor in mucosae and other compartments during the course of human immunodeficiency virus (HIV)-1 infection are poorly understood. To examine the impact of an acquired immunodeficiency syndrome virus on the gammadelta + T-cell population, rectal inoculation of macaques with simian immunodeficiency virus (SIV)-PBj14 was used as a model. After rectal inoculation, five macaques were sacrificed on days 4, 5, or 7 and then assessed for changes in the gammadelta T-cell receptor repertoire in different lymphoid compartments. There was decreased representation of gammadelta + T cells in the intestinal mucosae, blood, and spleens. Overall, the reduced number of total gammadelta + T cells was consistent with decreases in the Vgamma or Vdelta T-cell sub-populations. Nevertheless, there was no consistent deletion or expansion of a selected Vdelta + or Vdelta + cell sub-population. These results demonstrate that SIV-PBj14 replication and dissemination after mucosal inoculation resulted in a decline of detectable gammadelta + T cells, suggesting that macaque gammadelta + T cells are susceptible to down-regulation or destruction during acute SIV-PBj14 infection.
J Med Primatol 2000 Aug
PMID:Down-regulation of macaque gammadelta + T cells in lymphoid compartments after rectal infection with SIVsmmPBj14. 1108 76


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