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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Replication-competent molecular clones of feline immunodeficiency virus (FIV) were isolated directly from the DNA of bone marrow cells of a naturally FIV-infected cat. After transfection in a feline kidney cell line (CrFK) and subsequent cocultivation with peripheral blood mononuclear cells (PBMC), the viral progeny of the clones was infectious for PBMC but not for CrFK cells. PBMC infected with these clones showed syncytium formation, a decrease in cell viability, and gradual loss of CD4+ cells. The restriction maps of these clones differed from those obtained for previously described molecular clones of FIV derived from cats in the United States. The predicted amino acid sequence similarity of the envelope genes of the two clones was 99.3%, whereas the similarities of the sequences of the clones to those of two molecular clones from the United States, Petaluma and PPR, were 86 and 88%, respectively. Most of the differences between the amino acid sequences of the two clones and those of the clones from the United States were found in five different hypervariable (HV) regions, HV-1 through HV-5. The viral progeny of one of these clones was inoculated into two specific-pathogen-free cats. The animals seroconverted, and the virus could be reisolated from their PBMC.
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PMID:Isolation and partial characterization of infectious molecular clones of feline immunodeficiency virus obtained directly from bone marrow DNA of a naturally infected cat. 130 91

The long terminal repeat (LTR) of a retrovirus contains sequence elements that constitute a promoter for controlling viral gene expression in infected cells. We have examined regulation of LTR-directed gene expression in feline immunodeficiency virus (FIV), a T-lymphocytopathic lentivirus associated with a fatal AIDS-like disease in domestic cats. Two independent virus isolates, designated FIV-Petaluma and FIV-PPR, have been molecularly cloned and show greater than 85% sequence homology. Both clones (termed pF34 and pPPR) produce infectious virus after transfection of permissive feline cells. Basal promoter activity of the LTRs was measured in various cell lines in transient expression assays using plasmids containing the viral LTR linked to the bacterial chloramphenicol acetyltransferase gene. Both LTRs were strong promoters in several cell lines, although in some cell lines the pF34 LTR had four- to fivefold higher basal activity than the pPPR LTR. FIV LTR mutations affecting the first AP4 site, AP1 site, ATF site, or NF-kappa B site resulted in decreased basal activity of the FIV promoter. Mutational analysis also revealed a negative regulatory element. In cotransfection experiments, both pF34 proviral DNA and pPPR proviral DNA appeared to transactivate either the pF34 LTR or the pPPR LTR; however, levels of transactivation were very low. Cotransfection of both LTRs with FIV subgenomic clones containing various viral open reading frames resulted in low level or no transactivation. The LTRs of both FIV clones responded to cell activation signals in human T-lymphoid cells (Jurkat) treated with phytohemagglutinin and phorbol-12-myristate-13-acetate. Promoter function of both FIV LTRs was also enhanced in cells treated with either forskolin, an inducer of intracellular cyclic-AMP (c-AMP), or dibutyryl c-AMP. Analysis of site-specific mutants showed that a potential AP1 site in the U3 domain of the LTR was required for T-cell activation responses mediated by protein kinase C, whereas a putative ATF site was the target for c-AMP-induced responses mediated by protein kinase A. These studies revealed that cellular transcription factors play a significant role in regulation of FIV gene expression.
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PMID:Regulation of gene expression directed by the long terminal repeat of the feline immunodeficiency virus. 131 May 54

We have molecularly cloned the complete genomic DNA of TM2 strain of feline immunodeficiency virus (FIV) isolated in Japan and compared its nucleotide and the deduced amino acid sequence with those of previously described U.S. isolates, FIV Petaluma and FIV PPR. The infectious molecular clone of FIV TM2 is different from FIV Petaluma in host cell range; the clone can not infect Crandell feline kidney cells which were permissive for FIV Petaluma. The amino acid sequence homologies, in gag, pol, and env genes between FIV TM2 and Petaluma were 90%, 87%, and 81%, respectively. On the other hand, comparative analysis of each gene between FIV Petaluma and PPR showed 96,95, and 85%, respectively. These results suggested that the genomic diversity was present among FIV strains isolated from geographically distant areas. Interestingly, tat- and rev-like short open reading frames contained inframe stop codons in the FIV Petaluma but not in the FIV TM2.
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PMID:Molecular characterization and heterogeneity of feline immunodeficiency virus isolates. 131 25

The nucleotide sequences of the envelope (env) coding regions of two strains of the feline immunodeficiency virus isolated in Zurich, Switzerland (FIVZ1, FIVZ2) have been analysed. In addition, the complete sequence of the FIVZ1 isolate has been determined. Comparisons have been made with the previously published sequences of three North American isolates (PPR and the Petaluma strains FIV34TF10 and FIV14). The isolate FIVZ1 was very similar to the Petaluma strains of FIV and may represent a clonal derivative acquired by 'contamination'. Overall there are between 2.6% and 15.1% amino acid changes in the env gene products of the five isolates. Of the Zurich isolates, FIVZ2 exhibited the greatest divergence to the other viruses and based on its genotype, phenotype and origins probably represents a new isolate of FIV. Possibly the viruses diverged only recently from a common ancestor. Some 31 of the 33 cysteine residues and 17 of the 21 potential N-linked glycosylation sites of the FIV34TF10 env gene product were conserved among all five isolates. The open reading frame 3 (ORF3, or D) which overlaps the env gene (but is encoded in a different frame) has an ATG codon downstream of a potential splice acceptor site in all five isolates, supporting the view that it encodes a viral gene product. In ORF3 of FIVZ1 a stop codon was located 16 amino acids upstream of the stop codon of ORF3 of the other isolates. The ORF4 (or G) of isolate FIVZ2, thought to be the second coding exon of an FIV rev-like gene, contained a nucleotide deletion in amino acid 45 of ORF4, resulting in a--1 frameshift at this position. Comparison of the LTR sequences of the five isolates identified conserved promoter/enhancer elements. A potential stem-loop structure was identified in the R region of the LTRs of all the isolates, despite the heterogeneity of nucleotide sequences in that region. Such structures (TAR) are present in analogous regions of other lentiviruses and are responsible for tat-mediated trans-activation.
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PMID:Identification of conserved and variable regions in the envelope glycoprotein sequences of two feline immunodeficiency viruses isolated in Zurich, Switzerland. 166 Feb 15

The coding sequences of p17 and p24 of the Glasgow-8 strain of feline immunodeficiency virus (FIV) were amplified using the polymerase chain reaction and cloned into plasmid vectors. The predicted amino-acid sequences of FIV/Glasgow-8 p17 and p24 were compared with those of the Petaluma and PPR isolates of FIV. As seen with other retroviruses, these gag gene products are highly conserved, indicating that the protein products would be suitable antigens to detect anti-FIV antibodies in an immunoassay. Both p17 and p24 were stably expressed in Escherichia coli as fusion proteins with glutathione S transferase. A pure preparation of each fusion protein was obtained from induced bacterial lysates by affinity chromatography using glutathione-agarose beads. These recombinant proteins were used in an enzyme-linked immunosorbent assay to detect antibodies directed against FIV p17 and p24 in cat sera. This assay allows the identification of seropositive cats following infection with FIV and has greater sensitivity and specificity than a currently available immunodiagnostic test.
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PMID:Immunodiagnosis of feline immunodeficiency virus infection using recombinant viral p17 and p24. 166 75

Two molecular clones of feline immunodeficiency virus were compared. The first clone, 34TF10, was from a Petaluma, Calif., isolate; the second, PPR, was isolated from a cat in the San Diego, Calif., area. The cats from which the isolates were obtained suffered from chronic debilitating illnesses. The two molecular clones differed in their in vitro host cell range. The 34TF10 clone infected the Crandall feline kidney and G355-5 cell lines, but replicated less efficiently on feline peripheral blood leukocytes. In contrast, the PPR clone productively infected the primary feline peripheral blood leukocytes but not Crandall feline kidney or G355-5 cells. The 34TF10 and PPR clones had an overall sequence identity of 91%. The env gene was the least conserved (85% at the amino acid level). Additionally, the potential open reading frame for a Tat-like protein, ORF 2, contained a stop codon in the 34TF10 isolate which was not found in the PPR clone. This truncation did not prevent in vitro or in vivo replication of 34TF10. Two splice acceptor sites were identified in the 34TF10 clone. One was 5' to the beginning of the putative tat open reading frame, and the other was 5' to the putative vif product. Both of these acceptor sites were conserved in the PPR clone. The long terminal repeats of the viruses were 7% divergent between the two clones, with a lack of conservation in putative NF-kappa B, LBP-1, and CCAAT enhancer-promoter sites.
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PMID:Comparison of two host cell range variants of feline immunodeficiency virus. 169 7

Feline immunodeficiency virus (FIV) encodes the enzyme deoxyuridine-triphosphatase (DU; EC 3.6.1.23) between the coding regions for reverse transcriptase and integrase in the pol gene. Here, we report the in vivo infection of cats with a DU- variant of the PPR strain of FIV and compare its growth properties and tissue distribution with those of wild-type FIV-PPR. The results reveal several important points: (i) DU- FIV is able to infect the cat, with kinetics similar to that observed with wild-type FIV; (ii) both wild-type and DU- FIV-infected specific-pathogen free cats mount a strong humoral antibody response which is able to limit the virus burden in both groups of animals; (iii) the virus burden is reduced in the DU- FIV-infected cats, particularly in tissues such as spleen and salivary gland; and (iv) the mutation frequency in DU- FIVs integrated in the DNA of primary macrophages after 9 months of infection is approximately 5-fold greater than the frequency observed in DU- FIV DNA integrated in T lymphocytes. Mutation rate with wild-type FIV remains the same in both cell types in vivo. The dominant mutations seen in macrophages with DU- FIV are G-->A base changes, consistent with an increased misincorporation of deoxyuridine into viral DNA of DU- FIVs during reverse transcription. Because this enzyme is absent from human immunodeficiency virus type 1 and other primate lentiviruses, virus replication in cell environments with low DU activity may lead to increased mutation and contribute to the rapid expansion of the viral repertoire.
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PMID:Increased mutation frequency of feline immunodeficiency virus lacking functional deoxyuridine-triphosphatase. 763 16

The T-lymphotropic lentivirus, feline immunodeficiency virus (FIV) is now recognised as a major viral pathogen affecting domestic cat populations worldwide. A rapid, autologous red cell agglutination test for antibodies to FIV has been developed. A synthetic peptide analog corresponding to the immunodominant epitope within the FIV transmembrane glycoprotein gp40 residues (680-715) KVEAMEKFLYTAFAMQELGC (Acm)NQNQFFK(BrAc)KIPLELWTR was conjugated to an anti-feline erythrocyte antibody using a thio-ether linkage. Within 3 min of adding this reagent to 20 microliters of whole blood, circulating antibody to the peptide epitope caused agglutination of the red blood cells. The performance of this simple test is comparable with the two commercially available enzyme immunoassay (EIA) kits and an EIA based on this peptide. A variant of the gp40 (680-715) peptide corresponding to the FIV, PPR strain gp40 (678-716) sequence was also synthesised and no difference in reactivity was observed in an EIA on 211 seropositive samples, indicating that the peptide-based test may be applicable to other known strains of the virus.
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PMID:Autologous red cell agglutination test for antibodies to feline immunodeficiency virus. 781 59

Feline immunodeficiency virus (FIV) establishes persistent infections in cats inducing an acquired immunodeficiency syndrome. Differences in cell tropism have been observed among isolates of FIV (T. R. Phillips et al., J. Virol. 64, 4605-4613, 1990). The progeny of the infectious molecular clone of FIV p34TF10 was able to productively infect a feline fibroblast cell line, Crandell feline kidney cell, (CrFK), while the progeny of the molecular clone pPPR was not. However, pPPR, after transfection of CrFK cells, did produce virions which were able to productively infect feline lymphocytes. To analyze the mechanisms responsible for such differences in tropism and particularly the role of the envelope glycoproteins (Env), Env expression vectors were constructed by deletion of gag and pol genes from 34TF10 and PPR proviral clones. Env expression and function were studied by using a syncytium-formation assay and a quantitative ELISA. After transfection of CrFK, both 34TF10 and PPR Env precursors were correctly processed and Env surface glycoprotein, gp100, was released in culture supernatants. However, the Env of 34TF10 caused a dramatic syncytial effect in CrFK cells, while PPR Env did not induce any syncytium formation. The Env of 34TF10 placed under the control of the long terminal repeat of PPR maintained its ability to induce CrFK fusion. These results suggest that the inability of FIV PPR to infect CrFK fibroblasts is related to a restriction of virus entry mediated by the viral envelope.
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PMID:Differences in feline immunodeficiency virus host cell range correlate with envelope fusogenic properties. 785 93

Molecularly cloned viruses are considered essential reagents for characterizing viral domains responsible for infectivity and disease pathogenesis in the host. The infectivity and hematological alterations associated with two molecularly cloned isolates of feline immunodeficiency virus (FIV-pPPR and FIV-pF34) and an uncloned isolate (FIV-PPR) were assessed by inoculation of cats. Inoculated cats were tested for viral antibody, viremia, and clinical pathological disease. Peripheral blood mononuclear cells isolated from inoculated cats were assayed for virus infection by virus isolation, amplification of proviral DNA (by polymerase chain reaction), and in situ hybridization for viral RNA. Over 50% of the cats inoculated with cloned virus FIV-pF34 failed to seroconvert even when coinfected with feline leukemia virus; these cats were consistently virus positive only by amplification of proviral DNA. All cats inoculated with cloned virus FIV-pPPR seroconverted and were found virus positive by at least two of three virus detection assays. Both cloned viruses were less capable of suppressing CD4:CD8 ratios when compared to the biological isolates from which they were cloned. Isolates which replicate efficiently in feline peripheral blood mononuclear cells (PBMC), i.e., FIV-pPPR or biological FIV-PPR, caused greater virus load and lower CD4:CD8 ratios when compared to cloned FIV-pF34, which replicates efficiently in feline adherent cell lines and macrophages but poorly in primary feline PBMC. Molecular clones FIV-pF34 and FIV-pPPR will be useful reagents for characterization of viral determinants of virus load and possibly, cell tropism in vivo.
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PMID:Infection of cats with molecularly cloned and biological isolates of the feline immunodeficiency virus. 797 56


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