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)

The complete nucleotide sequence of the RNA genome of Jembrana disease virus (JDV), a lentivirus that causes an acute disease syndrome in Bali cattle (Bos javanicus), is reported. In addition to the gag, pol and env genes and flanking long terminal repeats (LTRs) that characterize all retroviruses, a number of accessory genes represented by small multiply spliced ORFs in the central and 3'-terminal regions of the genome, including tat and rev that are typical of lentiviruses, were identified. The genome of JDV was 7732 bp in length, 750 bp smaller than the genome of bovine immunodeficiency virus (BIV) strain BIV127. A striking feature of the genome was the many deletions relative to BIV127, the largest of which were 471 bp from the env gene and 157 bp from the U3 (promoter) region in the LTR. There were also several insertions of up to 33 bp in the JDV genome relative to BIV127 found in the env gene and small ORFs that overlap env. Other significant genomic differences between JDV and BIV127 included changes to cis-acting sequences throughout the genome such as promoter and enhancer sequences in the LTR, the trans-activation response region, splice sites and frameshift sequences; alterations to the gag precursor protein cleavage sites and thus the processed products; loss of the vpw and vpy ORFs; and amino acid changes in all coding regions. The significance of these changes is discussed in relation to the differences in pathogenicity between JDV and BIV.
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PMID:Nucleotide sequence analysis of Jembrana disease virus: a bovine lentivirus associated with an acute disease syndrome. 904 70

Pulmonary tuberculosis is a major complication of human immunodeficiency virus (HIV) infection. The radiographic manifestations of pulmonary tuberculosis in HIV-infected patients are not typical of those seen in immunologically normal individuals. We sought to determine whether these manifestations provide clues to the pathogenesis of tuberculosis in HIV-infected persons. The radiographic manifestations of pulmonary tuberculosis were reviewed and classified in 82 HIV-positive and 53 HIV-negative tuberculous patients in Gulu, Uganda. Pulmonary presentations of tuberculosis were more acute in HIV-positive patients, and often included hilar or mediastinal adenopathy and pleural effusions, findings typical of primary tuberculosis in immunologically normal individuals. Many patients also had chronic forms of tuberculosis, either alone or in combination with acute disease. The findings of this study support the hypothesis that reactivation of latent infections and progression of pre-existent chronic disease produce a substantial portion of the tuberculosis burden of HIV-positive persons in Uganda. Tuberculosis control efforts should extend beyond efforts at decreasing transmission of new infections.
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PMID:Radiology of pulmonary turberculosis and human immunodeficiency virus infection in Gulu, Uganda. 907 94

By animal-to-animal passage in macaques we derived a pathogenic chimeric simian-human immunodeficiency virus (SHIV) that caused CD4+ T cell loss and AIDS in pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the intravaginal and intravenous routes. On the basis of the outcome of infection and patterns of CD4+ T cell loss and viral load, disease was classified into four patterns: acute, subacute, chronic, and nonprogressive infection. During the study period, 15 of the 20 animals developed fatal disease, including AIDS, encephalitis, pneumonia, and severe anemia. Opportunistic pathogens identified in these animals included Pneumocystis, cytomegalovirus, Cryptosporidium, Toxoplasma, and Candida. No single parameter by itself predicted outcome, although a combination of low CD4+ T cell counts in blood, high plasma virus levels, and presence of autoantibodies to red blood cells reliably predicted a fatal outcome. Five animals (25%) died within 3 months of inoculation and constituted the group with acute disease, whereas the nine animals (45%) with subacute disease died between 3 and 8 months postinoculation. This 70% mortality within 8 months is significantly shorter than in HIV-1-infected human beings, of whom 70% develop fatal disease a decade after infection. SHIV infection in macaques provides a useful model with which to evaluate antiviral strategies, combining all the advantages of the SIVmac system, yet using a virus bearing the envelope gene of HIV-1.
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PMID:Characterization of the pathogenic KU-SHIV model of acquired immunodeficiency syndrome in macaques. 916 32

Viral infections may induce an acquired form of immunodeficiency, generally lasting a few weeks. In the more severe form, such as HIV infection, the immunodeficiency is permanent. Programmed death of T cells represents one of the mechanisms by which HIV determines the T cell functional impairment, finally resulting in the destruction of T cells. In this study, we evaluated whether an altered regulation of apoptosis was also implicated in the anergy associated with the common measles or varicella-zoster virus (VZV) infections in infancy. A spontaneous apoptosis of peripheral blood mononuclear cells was observed in children who had suffered from these infections as long as 6 mo after the acute disease. Apoptosis was demonstrated through analysis of cellular DNA content, morphologic evidence of cell nuclei shrinkage, and by analysis of DNA degradation. Stimulation of T cells through anti-CD4 MAb increased the number of apoptotic cells with a maximal effect 72 h after the stimulation. Our results suggest that apoptosis may account for the anergy that follows acute viral infections in infancy.
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PMID:Apoptosis as a mechanism of peripheral blood mononuclear cell death after measles and varicella-zoster virus infections in children. 943 16

Two chimeric proviruses comprising the U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9 in addition to other genomic regions of SIVagm3mc from African green monkeys (Cercopithecus aethiops) were constructed. The derived chimeric viruses (SIVagm3mc/SIVsmmPBj1.9) were both able to replicate in nonstimulated peripheral blood leukocytes from pig-tailed macaques (Macaca nemestrina), a biological property often correlated with acute pathogenicity. However, only one of the chimeric viruses was acutely pathogenic, inducing a rapid depletion of the peripheral CD4+ T cells in two infected pig-tailed macaques within 10 days after infection in a manner similar to infection with SIVsmmPBj1.9 itself. The other chimeric virus actively replicated during the first 8 weeks after experimental infection of two pig-tailed macaques but induced neither acute disease nor CD4+ T-cell depletion for 113 weeks after infection. Thus, the U3 promoter and the nef gene of SIVsmmPBj1.9 alone appear to be insufficient to confer acute pathogenicity to SIVagm3mc.
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PMID:The U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9 do not confer acute pathogenicity upon SIVagm. 952 79

The variant simian immunodeficiency virus termed SIVsmmPBj14 induces a rapidly fatal disease in pig-tailed macaques. The acute pathogenic effects of this virus appear to be associated with at least two in vitro characteristics: the ability to induce lymphocyte proliferation; and the ability to replicate in unstimulated PBMC. Two of the amino acids in Nef of PBj14 (the No. 17 residue, tyrosine, and the No. 18 residue, glutamic acid) appear to be linked to the virus' ability to induce lymphocyte activation. To further study the effects of these amino acids on PBj14-induced pathogenesis, we generated two mutant viruses from our molecular clone, PBj6.6, containing either changes in both the No. 17 and No. 18 residues (termed PBj6.6YE-RQ), or a single change in the No. 17 residue (termed PBj6.6Y-R). In vitro analyses of these viruses showed that while their replicative abilities in stimulated peripheral blood mononuclear cells (PBMC) were altered, they still maintained the ability to replicate in unstimulated PBMC. Replication of these viruses in macrophage populations was impaired relative to the wild-type virus. Both mutant viruses were unable to induce proliferation of macaque PBMC in vitro. Virus derived from PBj6.6Y-R was unable to induce acute disease in macaques, but did maintain the ability to induce lymphopenia and intestinal lymphoid hyperplasia. These results show that the tyrosine-17 residue of Nef is linked to lymphocyte proliferation and disease development, but also suggest that the pathogenic characteristics of SIVsmmPBj14 are dependent upon multiple genetic determinants.
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PMID:The tyrosine-17 residue of Nef in SIVsmmPBj14 is required for acute pathogenesis and contributes to replication in macrophages. 960 97

The molecularly cloned viruses known as SIVmac239/R17Y and SIVmac239/YEnef cause extensive lymphocyte activation and induce an acute disease syndrome in macaque monkeys. One manifestation of this syndrome is a severe diffuse cutaneous maculopapular exanthem that is similar to the exanthem associated with HIV-1 infection. To examine the pathogenesis of this exanthem, biopsies obtained throughout the course of clinically evident rash were examined for the presence of virus by in situ hybridization and immunohistochemistry, and the cellular infiltrate was characterized with respect to cellular immunophenotype and chemokine receptor expression. The onset of rash was associated with abundant simian immunodeficiency virus nucleic acid and protein within perivascular dermal infiltrates and occasionally within intraepithelial cells. Analysis of cellular infiltrates showed that biopsies, obtained on the day of rash onset, were composed of equal numbers of CD4+ and CD8+ lymphocytes and abundant alphaEbeta7 positive cells surrounding vessels with upregulated endothelial E-selectin. Moreover, by examining virus expression in sequential skin biopsies from the same animal, the clearance of virus and the resolution of rash were associated with an increase in the percentage of cells expressing CD8, the chemokine receptor CXCR3, and GMP-17, a marker of cytotoxic granules. These results suggest that activated cytotoxic T cells are trafficking to sites of inflammation in the skin and directly or indirectly affect levels of viral replication at these sites.
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PMID:Characterization of the cutaneous exanthem in macaques infected with a Nef gene variant of SIVmac239. 962 Feb 96

Simian immunodeficiency virus strain PBj14, SIVsmmPBj14, is unique among primate lentiviruses in its ability to trigger the proliferation of resting simian lymphocytes and to cause the rapid death of experimentally inoculated pigtailed macaques. Severe enteropathy, immune activation, and extensive apoptosis, particularly within gut-associated lymphoid tissue, characterize the acute disease syndrome associated with SIVsmmPBj14 infection. In the present study, we examined whether the ability of this virus to cause widespread apoptosis might be linked to the up-regulation of Fas ligand (CD95L) expression in virally infected cells. In vitro studies revealed that expression of the viral Nef protein, in the absence of any other viral gene product, was sufficient to up-regulate the transcriptional activity of the CD95L promoter and to cause cell surface expression of Fas ligand. This up-regulation was NFAT dependent (inhibited by cyclosporin A) and did not occur in cells that expressed a mutated derivative of the viral Nef protein, lacking a previously defined immunoreceptor tyrosine-based activation motif. These findings were corroborated by analysis of tissue sections from virally infected macaques. Immunohistochemical staining revealed that Fas ligand expression was efficiently up-regulated in the GALT of animals that had been experimentally infected with wild-type SIVsmmPBj14 but not in animals that were infected with a nonacutely pathogenic viral mutant lacking the Nef ITAM. Taken together, these results suggest that the ability of SIVsmmPBj14 to cause acutely lethal disease and to up-regulate FasL expression may be linked. Additional studies will be required to determine whether the induction of FasL expression is in itself important for acute disease pathogenesis.
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PMID:Induction of fas ligand expression by an acutely lethal simian immunodeficiency virus, SIVsmmPBj14. 987 14

During 14 months of infection of a pig-tailed macaque, the acutely lethal simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) evolved from the minimally pathogenic strain SIVsmm9. The virus isolated at 8 months (SIV-PBj8) exhibited properties of both SIVsmm9 and SIV-PBj14, indicating that a phenotypic transition occurred between 6 and 10 months. To assess the influence that this new composition of biologic properties might have on pathogenicity, three pig-tailed macaques were inoculated intravenously with SIV-PBj8. Although no animals developed the severe acute disease syndrome typical of SIV-PBj14, all had high levels of viremia and died of AIDS at 4, 10. 5, and 32 months. Characterization of the SIV-PBj8-derived quasispecies that evolved in these macaques showed that at 4 days after inoculation, viruses from all three animals exhibited in vitro properties different from those of the inoculum. By 4 months, the initial phenotypic profiles had changed, with the quasispecies in plasma from the animal (J90232) that died at this time most closely resembling SIV-PBj14, not SIV-PBj8. Phylogenetic trees of the gp41/Nef region of viruses in 4-month plasma from J90232 revealed three distinct populations with high bootstrap values: one group branched with SIVsmm9, one with SIV-PBj14, and one with SIV-PBj8 (ratio of clones, 5:9:5). Nucleotide sequence analysis suggested that some members of the original SIV-PBj8 quasispecies may have been evolving toward a SIV-PBj14-like genotype at the time macaque J90232 died. The use of SIV-PBj8, which was more pathogenic than SIVsmm9, but less pathogenic than SIV-PBj14, may provide the optimal genetic background on which to identify the minimal, multigenic determinants of the SIV-PBj14 phenotype. The results of our studies on SIV-PBj14 indicate that in some, but not all, cases of primate lentivirus infection more pathogenic variants evolve, selectively proliferate, and more than likely contribute to disease progression.
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PMID:Pathogenicity and comparative evolution in vivo of the transitional quasispecies SIVsmmPBj8. 1036 1

We report that simian immunodeficiency virus (SIV) infection in macaques is a valuable animal model for studying post-exposure chemoprophylaxis (PECP). PECP with the acyclic nucleoside reverse transcriptase inhibitors 9-(2-phosphonylmetho-xyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) at early viral infection can provide long-term protection against subsequent heterologous SIV challenge. Eight macaques previously treated with PECP (called PECP macaques) and four naive controls were challenged intravenously with the most virulent form of SIV, SIV(PBj14). All controls showed signs of SIV(PBj14)-induced acute disease syndrome on days 6 and 7 post-inoculation (PI). One had a fatal viral infection and two surviving controls had persistent infection and decreased CD4+ cell count. Virologic studies of the three surviving controls revealed SIV in multiple lymphoid tissues and peripheral blood mononuclear cells (PBMCs) at necropsy. In contrast, the PECP macaques showed none to mild signs of acute disease syndrome at day 9 PI and exhibited only transient SIV infection in PBMCs between weeks 1 and 8 PI. In virologic studies of five PECP macaques necropsied, two macaques were SIV-negative and the other three were SIV-positive only in either lymph node or bone marrow. Three SIV(PBj14)-challenged PECP macaques, that were randomly reserved for a follow-up study for > 4.0 years PI showed extremely low to undetectable levels of PBMC-associated viremia and normal to increased levels of CD4 + and CD8 + cell counts throughout the study. Our results indicate that early PECP could activate immune responses to protect against subsequent infection with heterologous challenge virus.
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PMID:Post-exposure chemoprophylaxis (PECP) against SIV infection of macaques as a model for protection from HIV infection. 1108 87


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