Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 immune response against human immunodeficiency virus type-1 (HIV-1) is believed to play a role in controlling the early stages of disease progression. The cellular immune response, in particular cytotoxic T lymphocyte (CTL) activity, may be important for eliminating virally infected cells in HIV-1-infected individuals. Genetic immunization using retroviral vectors provides an effective means of introducing antigens into the antigen presentation pathways for T cell stimulation. A nonreplicating, amphotropic murine retroviral vector containing the HIV-1 IIIB env gene has been used to transduce primary rhesus monkey fibroblasts for the expression of HIV-1 antigenic determinants. Rhesus monkeys were immunized with four doses of either vector-transduced autologous fibroblasts (VTAF) expressing the HIV-1 IIIB ENV/REV proteins or nontransduced autologous fibroblasts (NTAF) administered at 2-week intervals. The animals were evaluated for both the induction of HIV-1-specific immune responses and potential toxicity associated with this ex vivo treatment. The VTAF-immunized monkeys generated CTL responses specific for HIV-1 ENV/REV expressing autologous target cells, whereas, NTAF-immunized monkeys showed negligible CTL activity. The cytotoxic activity was mediated by CD8+, major histocompatibility complex (MHC)-restricted CTL. In addition, antibody responses directed against the HIV-1 gp120 protein were also detected in the sera of VTAF-immunized monkeys. Clinical and histopathological evaluation of immunized monkeys showed no evidence of significant adverse events. Several animals that received either VTAF or NTAF had detectable anti-cytoplasmic antibodies, but were not positive for anti-nuclear antibodies or rheumatoid factor. Subsequent evaluation of renal, synovial, and hepatic tissue samples from these monkeys revealed no autoimmune disease-associated lesions. This study demonstrates the safety and ability of autologous retroviral vector-transduced cells expressing HIV-1 IIIB ENV/REV proteins to stimulate immune responses in a non-human primate model, and provides a basis for this form of genetic immunization in HIV-infected humans.
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PMID:Cytotoxic T lymphocyte and antibody responses generated in rhesus monkeys immunized with retroviral vector-transduced fibroblasts expressing human immunodeficiency virus type-1 IIIB ENV/REV proteins. 798 10

We have used the polymerase chain reaction (PCR) and direct sequencing of the amplified products to obtain information of the molecular nature of an FIV isolate, T637. Cats experimentally infected with T637 have progressed to clinical immunodeficiency disease. The 5' long terminal repeat (LTR), most of the genes coding for internal proteins (GAG) and surface proteins (ENV), and part of the polymerase (POL) gene have been sequenced. The LTR of T637 has 92% nucleic acid identity with the prototype strain, FIV-Petaluma and the Glasgow isolate, FIV-14, 89% with a Swiss isolate, FIVZ2, and 95% with the PPR isolate. Both GAG and POL genes of T637 share extensive homology with Petaluma and PPR. In the ENV gene, T637 has 91% nucleic acid homology with Petaluma and 86% with PPR, and an overall amino acid homology of between 81-87%. For the surface (SU) region of the ENV gene product, T637 has 89% amino acid homology with Petaluma and FIVZ2 and 86% with PPR.
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PMID:Polymerase chain reaction and partial sequencing of a British isolate (T637) of feline immunodeficiency virus. 827 81

The evolution of the virus-specific cytotoxic T-lymphocyte response in two cats experimentally infected with feline immunodeficiency virus (FIV) was monitored. Effector cells were derived from peripheral blood lymphocytes during the acute and chronic phases of infection (0 to 21 and 62 to 127 weeks, respectively) and from the spleen and lymph nodes at 127 weeks after infection. Lymphocytes were restimulated in vitro with paraformaldehyde-fixed, autologous lymphoblasts which had been infected with recombinant vaccinia viruses expressing FIV GAG or ENV proteins. Unstimulated lymphocytes were also used as effectors in some assays. 51Cr-labelled autologous skin fibroblasts infected with recombinant vaccinia viruses were used as targets. FIV GAG-specific cytotoxic precursors were detected in restimulated circulating lymphocytes during acute infection in both cats. The onset of this activity was as early as 2 weeks postinfection (p.i.) in one cat. From 62 weeks p.i. neither FIV GAG- nor ENV-specific precursors could be detected in the peripheral blood. However, at 127 weeks p.i., GAG- and ENV-specific cytotoxic precursors were detected in lymphocytes isolated from lymph nodes. The FIV-specific cytotoxic cells were predominantly major histocompatibility complex class I restricted. No cytotoxic activity was detected from unstimulated lymphocytes. These studies demonstrate the use of an assay system for dissecting the FIV-specific cytotoxic cell response and show that precursor cells appear in the circulation very early after infection and prior to a detectable antibody response. Our results also suggest that the persistent high-level circulating antiviral cytotoxic T-lymphocyte responses seen in human immunodeficiency virus-infected humans may not be a feature of FIV infections in cats.
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PMID:A longitudinal study of feline immunodeficiency virus-specific cytotoxic T lymphocytes in experimentally infected cats, using antigen-specific induction. 870 46

The detection of specific antibodies against human immunodeficiency virus (HIV) was tested by dot blot enzyme immunoassay in 95 urine samples from 72 individuals infected with HIV and 23 seronegative individuals. Western blot of paired serum samples from these same individuals was used as the gold standard. The dot blot tested had a sensitivity of 97.2% and a specificity of 100%; only two samples from HIV-infected individuals at Centers for Disease Control (CDC) stages II and IV were non-reactive. Reactive and discrepant samples (serum/urine) were confirmed by Western blot, which had a sensitivity of 98.6% and a specificity of 100%. The most commonly observed Western blot reactivity pattern in urine samples included bands against three groups of HIV structural proteins (ENV, POL, and GAG). The results indicate that urine can be used in screening for HIV antibodies in epidemiological studies of high-prevalence populations, though it is not recommended for individualized diagnostic purposes.
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PMID:Urine samples as a possible alternative to serum for human immunodeficiency virus antibody screening. 895 May 59

The complete nucleotide sequence of the integrase (IN) protein coding region of the murine leukaemia virus (MLV) amphotropic strain 4070A is presented. The sequence comprises 1,224 nucleotides, encoding a 408-residue polypeptide of M(r) 46,312. Alignment of the inferred 4070A IN amino acid sequence with the IN proteins of other MLV showed that substitutions are confined largely to segments within the N- and C-terminal domains. In the N-terminal domain the majority of substitutions occur as contiguous 2- to 6-residue blocks, whereas in the C-terminal domain they occur as isolated entities except within a short segment characterized by deletions/insertions. Selection appears to act on the C-terminal 19 residues of IN rather than on the N-terminal residues of ENV (encoded by overlapping reading frames), suggesting a functional role for this segment. Phylogenetic analyses grouped the sequences into two clusters, one comprising IN from the amphotropic strain 4070A and three ecotropic MLV (CAS-BR-E, Moloney and Friend), the other consisting of IN from three ecotropic MLV (two radiation-induced viruses and AKV) and a mink cell focus-forming (MCF) MLV virus. The same dichotomy and cluster composition was obtained from analysis of the long terminal repeat (LTR) regions from these viruses (consistent with the functional interrelationship of IN and LTR) but not from analysis of envelope protein sequences (consistent with the functional independence of ENV proteins from both IN and LTR). Secondary structure predictions supported features determined from the catalytic domain of human immunodeficiency virus and avian sarcoma virus IN, and identified probable structures within the relatively long N- and C-terminal domains of MLV IN proteins.
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PMID:Nucleotide sequence of the murine leukaemia virus amphotropic strain 4070A integrase (IN) coding region and comparative structural analysis of the inferred polypeptide. 967 35

The aim of the present study was to evaluate the possible utilization of saliva and urine as alternative samples to serum for the diagnosis of human immunodeficiency virus (HIV) infection. A total of 302 individuals participated in the study: 187 HIV-infected individuals (106 had Centers for Disease Control and Prevention [CDC] stage II infection, 19 had CDC stage III infection, and 62 had CDC stage IV infection) and 115 noninfected persons (46 of the noninfected persons were blood donors and 69 belonged to a group at high risk of HIV infection). Paired saliva and urine samples were taken from each of the participants in the study. The presence of HIV-specific antibodies was detected by an enzyme-linked fluorescent assay (ELFA), and the result was confirmed by Western blot analysis (WB). The ELFA with saliva gave maximum sensitivity and specificity values, while ELFA had lower sensitivity (95.2%) and specificity (97. 4%) values for detection of HIV antibody in urine samples. WB with all saliva samples fulfilled the World Health Organization criterion for positivity, while only 96.8% of the urine samples were confirmed to be positive by WB. Among the four reactivity patterns found by WB of these alternative samples, the most frequent included bands against three groups of HIV structural proteins (was ENV, POL, and GAG). The reactivity bands most frequently observed were those for the proteins gp160 and gp120. The least common reactivity band was the band for protein p17. The detection of HIV antibodies in saliva samples by means of ELFA with the possibility of later confirmation by WB makes saliva an alternative to serum for possible use in the diagnosis of infection. In contrast, HIV antibody detection in urine samples by the same methodology (ELFA) could be taken into consideration for use in epidemiological studies.
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PMID:Human immunodeficiency virus antibody testing by enzyme-linked fluorescent and western blot assays using serum, gingival-crevicular transudate, and urine samples. 1007 32

Human (H-) CCR5 is the primary coreceptor for ENV-mediated fusion by R5 strains of human immunodeficiency virus type 1, whereas mouse (M-) CCR5 lacks this function. An array of 23 H/M-CCR5 hybrids containing increasing amounts of H-CCR5 extending from the N terminus generated by random chimeragenesis had a biphasic pattern of coreceptor activity with JRFL and 89.6, revealing active regions in the N-terminal extracellular domain (N-ED) and at the junction of cytoplasmic loop 3. The M-CCR5 mutant in which divergent residues were replaced with the corresponding H-CCR5 N-ED sequence (NyYTsE) gained coreceptor function in fusion but not infection experiments. A M-CCR5 double mutant with substitution of human sequences for divergent residues from the N-ED and cytoplasmic loop 3 had augmented coreceptor activity in fusion assays and gain of function in infection experiments. The SIV-251 ENV utilized H- and M-CCR5 and variants. Flow cytometric analysis of M-CCR5 mutants and bifunctional receptors composed of CD4 domains fused to M-CCR5 mutants excluded the possibility that differences in coreceptor activity resulted from variations in cell surface expression. These results demonstrate that the coreceptor activity of the H-CCR5 N-ED is modulated by intracellular residues, illustrating the complexity of CCR5 requirements for interaction with ENV.
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PMID:CCR5 HIV-1 coreceptor activity. Role of cooperativity between residues in N-terminal extracellular and intracellular domains. 1049 2

At the initial stage of retroviral infection, virion envelope glycoprotein (env product) binds to cell surface receptors. Cells infected with retrovirus or into which the env gene was introduced, become resistant to superinfection by other retroviruses with the same receptor specificity, a phenomenon known as receptor interference. We have demonstrated previously that the introduction of an env gene from a truncated endogenous ecotropic murine leukemia virus (MuLV), the Fv-4 resistance (Fv-4r) gene, into the bone marrow hematopoietic cells of Fv-4 sensitive (Fv-4s) mice protected mice from ecotropic retrovirus-induced disease. Using the gene transfer system under the control of the retroviral vector and bone marrow transplantation (BMT), here we could show that the expression of an introduced Fv-4r gene in hematopoietic cells continued for more than 1 year after BMT. To determine the inhibitory mechanism of Fv-4r env gene expression against FLV-infection in this model system, peripheral blood mononuclear cells (PBMCs), or spleen cells from chimeras with various degrees of env-expression, were mixed with green fluorescence protein (GFP)-conjugated Friend MuLV envglycoprotein (GFP-Fr-ENV). The amount of GFP-Fr-ENV bound to these cells inversely correlated with the expression intensity of the transduced env gene indicating the receptor interference effect. Next, to see whether transduction of the Fv-4r gene would protect an immunosuppressed host from FLV-induced leukemogenesis, we generated immunocompromised chimeras by transplanting env-transduced bone marrow cells into a thymectomized host. These chimeras also resisted FLV-induced leukemogenesis, indicating that receptor interference-based gene therapy could become a therapeutic basis for immunodeficiency virus-induced diseases in vivo.
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PMID:A gene therapy model for retrovirus-induced disease with a viral env gene: expression-dependent resistance in immunosuppressed hosts. 1168 21

Venezuelan equine encephalitis (VEE) virus-replicon particles (VRP) were used to generate feline immunodeficiency virus (FIV) Gag- and ENV-expressing vaccine vectors. Serum and mucosal FIV-specific antibody was detected in cats immunized subcutaneously, once monthly for 5 months, with FIV-expressing VRP. Expansion of the CD8+ L-selectin negative phenotype and transient CD8+ noncytolytic suppressor activity were seen in cats immunized with FIV-expressing or control VRP. Despite induction of FIV-specific immune responses and nonspecific suppressor responses, all cats became infected following vaginal challenge with high dose, pathogenic cell-associated FIV-NCSU(1) although relative early maintenance of CD4+ cells was seen in FIV-immunized cats.
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PMID:Evaluation of FIV protein-expressing VEE-replicon vaccine vectors in cats. 1245 Jul 1

Genome-wide screening of sequence databases for human endogenous retroviruses (HERVs) has led to the identification of 18 coding env genes, among which two-the syncytin genes-encode fusogenic ENV proteins possibly involved in placenta physiology. Here we show that a third ENV, originating from the most "recent" HERV-K(HML2) family, is functional. Immunofluorescence analysis of env-transduced cells demonstrates expression of the protein at the cell surface, and we show that the protein confers infectivity to simian immunodeficiency virus pseudotypes. Western blot analysis of the pseudotyped virions further discloses the expected specific cleavage of the ENV precursor protein. This functional ENV could play a role in the amplification--via infection of the germ line--of the HERV-K genomic copies, all the more as coding HERV-K gag and pol genes can similarly be found in the human genome, which could therefore generate infectious virions of a fully endogenous origin.
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PMID:Identification of a functional envelope protein from the HERV-K family of human endogenous retroviruses. 1630 28


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