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)

Visna virus is a pathogenic lentivirus of sheep that is distantly related to the primate lentiviruses, including the human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 in cell culture requires the expression of a virus-encoded protein, Tat, which is a potent trans-activator of viral gene expression. Visna virus encodes an analogous Tat protein that greatly increases gene expression directed by the visna viral LTR. This report uses a stable vero cell line that constitutively expresses visna virus Tat to investigate the molecular mechanism of action of Tat on viral gene expression. Transient expression assays, using the visna virus LTR to drive transcription of the bacterial gene for chloramphenicol acetyltransferase (CAT), demonstrate that Tat trans-activates gene expression by increasing steady-state mRNA levels. The increase in steady-state mRNA levels is sufficient to account for the increase in protein observed and is due, in part, to an increase in the rate of transcription initiation. Tat mediates the accumulation of mRNA through AP-4 and AP-1 binding sites located in the U3 region of the LTR. Deletion of the upstream AP-1 and AP-4 binding sites results in a residual low level of trans-activation by Tat. Further experiments, using LTRs with R-U5 sequences deleted to +10, demonstrate AP-1 and AP-4 mediated responses to TAT at the RNA level, but no increase was observed in CAT protein.
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PMID:Molecular mechanisms of visna virus Tat: identification of the targets for transcriptional activation and evidence for a post-transcriptional effect. 131 69

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of >> 1:1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus. 133 98

Visna virus encodes a posttranscriptional regulatory protein that is functionally analogous to the Rev trans activator of human immunodeficiency virus type 1. Here, we demonstrate that the known functional organization of the human immunodeficiency virus type 1 Rev trans activator is shared by the distantly related visna virus Rev protein. In particular, both Rev proteins contain an N-terminal domain marked by a highly basic core motif that determines RNA sequence specificity, as well as a second C-terminal domain containing an essential leucine-rich motif that functions as an activation domain. Chimeric proteins consisting of the binding domain of one Rev protein fused to the activation domain of the other were fully functional in the viral sequence context cognate for the binding domain. We also describe derivatives of visna virus Rev bearing a defective activation domain that displayed a trans-dominant negative phenotype in transfected cells. These visna virus Rev mutants may prove useful in the derivation of transgenic animals resistant to this agriculturally important retroviral pathogen.
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PMID:Conserved functional organization of the human immunodeficiency virus type 1 and visna virus Rev proteins. 164 96

Visna virus and human immunodeficiency virus are prototypes of animal and human lentiviruses, respectively, that persist and are disseminated despite the host immune response because cells in the tissues and the bloodstream harbor viral genomes in a covert state. To facilitate identification of these latently infected cells, the polymerase chain reaction has been adapted to amplify viral DNA in fixed cells for detection by in situ hybridization. By using a multiple primer set that generates DNA segments with overlapping cohesive termini, visna virus DNA can be amplified, retained, and detected in infected cells with sensitivities that exceed those of existing methods by more than 2 orders of magnitude. This advance in single-cell technology should prove useful in diagnosing and gaining insight into the pathogenesis of viral infections and provide new opportunities to look for viruses in chronic diseases of unknown etiology.
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PMID:Amplification and detection of lentiviral DNA inside cells. 216 14

Extremely low frequencies of CpG dinucleotides are found in the genomes of the lentivirus subfamily of retroviruses, including the human, simian and feline immunodeficiency viruses (HIV1, HIV2, SIV, and FIV, respectively), equine infectious anemia virus (EIAV), and the ovine lentivirus, Visna. The occurrence of CpG dinucleotides is greater in the 2-3 (NCG) than in the 1-2 (CGN) codon-defined frame, as well as in the gag and env genes, compared to the more conserved pol gene. These differences suggest that CpG depletion in lentiviruses occurs as a result of selection against CpG rather than due to mutational bias, the latter is responsible for low CpG frequencies in vertebrate genomes. CpG levels in the onco-retrovirus subfamily are reduced to a lesser extent, principally due to mutational bias. The difference between the retrovirus subfamilies appears to reflect their evolutionary origin, that is, lentiviruses have no known endogenous counterparts whereas most oncoviruses have endogenous cellular counterparts with which they can undergo recombination. Furthermore, we suggest that the number of CpG dinucleotides in a lentiviral genome determines the maximum potential DNA methylation level of the provirus, which in turn affects viral transcription in host cells.
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PMID:Selection against CpG dinucleotides in lentiviral genes: a possible role of methylation in regulation of viral expression. 217 Sep 45

Visna virus is an ungulate lentivirus that is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 and of other complex primate retroviruses, including human T-cell leukemia virus type I (HTLV-I), requires the expression in trans of a virally encoded post-transcriptional activator of viral structural gene expression termed Rev (HIV-1) or Rex (HTLV-I). We demonstrate that the previously defined L open reading frame of visna virus encodes a protein, here termed Rev-V, that is required for the cytoplasmic expression of the incompletely spliced RNA that encodes the viral envelope protein. Transactivation by Rev-V was shown to require a cis-acting target sequence that coincides with a predicted RNA secondary structure located within the visna virus env gene. However, Rev-V was unable to function by using the structurally similar RNA target sequences previously defined for Rev or Rex and, therefore, displays a distinct sequence specificity. Remarkably, substitution of this visna virus target sequence in place of the HIV-1 Rev response element permitted the Rev-V protein to efficiently rescue the expression of HIV-1 structural proteins, including Gag, from a Rev- proviral clone. These results suggest that the post-transcriptional regulation of viral structural gene expression may be a characteristic feature of complex retroviruses.
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PMID:Visna virus encodes a post-transcriptional regulator of viral structural gene expression. 217 Sep 81

Visna virus is a lentivirus which causes a slow progressive disease involving the immune system and the central nervous system. To determine the role of the viral long terminal repeat (LTR) in targeting the virus to specific host cells and tissues, transgenic mice were constructed which contained the visna virus LTR directing expression of the bacterial gene encoding chloramphenicol acetyltransferase (CAT). Analysis of the transgenic mouse tissues for CAT activity revealed that the viral LTR was responsible, in part, for the tropism of visna virus for macrophages and the central nervous system. Expression of the LTR required the macrophage to be in an activated state both in vivo and in vitro. Thioglycolate activation of peritoneal macrophages in vivo and 12-O-tetradecanoylphorbol 13-acetate treatment in vitro induced expression of the visna virus LTR. Lymphocytes from the spleens of the transgenic mice expressed CAT activity, suggesting that visna virus was able to replicate in lymphocytes, as did human immunodeficiency virus and simian immunodeficiency virus. These studies demonstrated that the lentivirus LTR was responsible, in part, for cell and tissue tropism in vivo.
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PMID:The visna virus long terminal repeat directs expression of a reporter gene in activated macrophages, lymphocytes, and the central nervous systems of transgenic mice. 253 92

Visna virus is the prototype lentivirus, with a genome structure similar to that of the human immunodeficiency viruses HIV-1 and HIV-2. We have analysed in vitro the transcription pattern of this virus in lytic infections of choroid plexus cells. Northern blot analysis shows the presence of spliced subgenomic mRNA species of 4.9, 4.3, 4.0, 1.7 and 1.4 kb. Use of appropriate subgenomic probes shows that the first three of these species encode envelope protein (but also potentially the small open reading frames Q and S). The 1.7 kb RNA could contain S. In order to elucidate the translational coding potential of the smallest RNA, and to characterize further all the transcripts, S1 mapping was performed across those parts of the genome which were close to exon/intron boundaries. This allowed the definition of acceptor splice sites following both introns 1 and 2 as well as donor sites preceding intron 2. The data suggest that the 1.4 kb RNA encodes a protein derived from the F reading frame that may form part of a precursor protein and also contains sequences with some degree of homology to the rev (trs/art) protein of HIV, as well as a typical protease cleavage site between these sequences and the F protein.
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PMID:A transcriptional map of visna virus: definition of the second intron structure suggests a rev-like gene product. 254 79

The complete nucleotide sequences of several human immunodeficiency virus 1 (HIV-1) genomes were converted by computer to respective H curves. These three-dimensional space curves embody all the information contained in the sequence due to their abstract vectorial structure. For one sequence (HIV-1 isolate BRU) special efforts were made to maximize the available resolution (the number of nucleotides visually discernible within a unit length of the curve) when making a hard, master copy of the H curve. Using a computergraphic/photographic hybrid process the 9191 nucleotides of this HIV-1 sequence were condensed into an H curve of only 37.1 cm vertical length. Although each 1-mm segment of this curve represented 25 nucleotide residues, each of the individual nucleotides of the entire sequence was still distinguishable upon direct inspection using a simple magnifying lens. Several functionally important loci of the HIV-1 sequence could be recognized on the H curve owing to characteristic line forms at corresponding locations. Utilizing H curves of lower resolution, the total nucleotide sequences of several different HIV-1 isolates and related viral sequences [Visna, equine infectious anemia (EIAV), Moloney murine leukemia (Mo-MLV), bovine leukemia (BLV), and human T-cell leukemia, type I (HTLV-I)] were visually compared side by side. An interesting similarity was noted between the location of the S3 fragment of the EIAV sequence and that of a relatively G-C rich region on the env portion of the HIV-1 sequences.
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PMID:DNA sequence (H) curves of the human immunodeficiency virus 1 and some related viral genomes. 340 11

Visna-maedi virus is a lentivirus that causes a chronic disease in sheep affecting, among other organs, the lungs. Interstitial pneumonitis is similar to that in man associated with the infection by the human immunodeficiency virus type-1. We have compared the pathological features of lungs of sheep naturally infected with visna-maedi virus with the results obtained from bronchoalveolar lavage and virus isolation. Semi-quantitative grading of the lesions was performed on 147 sheep lungs obtained from the slaughterhouse. Seventy-seven were macroscopically and histologically normal, 39 had typical lesions of interstitial lung disease (maedi), and 13 had minor lesions of the same type. Eighteen of the affected lungs were heavily infested with parasites. Of these parasite-infected lungs, 9 showed typical maedi lesions and 4 showed minor lesions; parasite infection had no obvious effect on the development of maedi. In keeping with pathological findings, bronchoalveolar lavage disclosed an alveolitis process in the maedi lungs with increased macrophage, lymphocyte and neutrophil numbers. Cytopathic virus was detected from alveolar macrophage coculture with fibroblasts more often from maedi lungs (10/12) than from normal lungs (9/39). Electron microscopy of bronchoalveolar lavage cocultures revealed typical lentiviral particles. Animals with minor lesions may be at an early stage of the disease.
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PMID:Lentivirus-induced interstitial lung disease: pulmonary pathology in sheep naturally infected by the visna-maedi virus. 795 50


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