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

Feline immunodeficiency virus (FIV) gag gene was expressed in baculovirus vectors to investigate its potential for the assembly of virus-like particles. The unprocessed 50-kDa FIV gag precursor made in infected insect cells by recombinant AcFIVGAG-1 was myristoylated, assembled at the cell surface into virus-like particles (with diameters of approximately 100 nm), and efficiently released into the culture supernatant fluids. The presence of the complete viral-coded protease component of the FIV pol gene engineered into a second expression vector (AcFIVGAG-P5) resulted in the efficient processing of the gag precursor to its component proteins and abolished particle formation and secretion. Insertion of a stop codon in this vector upstream of the putative gag-pol frameshift site (GGGAAAC) resulted in the derivation of an expression vector (AcFIVGAG-R) that made a truncated, unprocessed 46-kDa FIV gag precursor lacking some 34 amino acids in the p10 carboxy-proximal coding region of gag. This vector synthesized tubular structures in the cytoplasm of infected cells and released them into the cell supernatant. The results demonstrate that the FIV gag precursor can spontaneously assemble into virus-like particles without any other virus proteins and that the carboxy-terminal part of the precursor gag protein is essential for such assembly.
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PMID:Analyses of the requirements for the synthesis of virus-like particles by feline immunodeficiency virus gag using baculovirus vectors. 164 71

We have cloned the simian foamy virus type 1 genome (SFV1) and determined its nucleotide sequence. Analysis of this genome reveals, in addition to the usual genes encoding retroviral capsid, reverse transcriptase, and envelope protein (respectively, gag, pol, and env), two open reading frames (ORFs) between env and the long terminal repeat with partial homology to the human foamy virus (HFV) bel1 and bel2 genes. The first ORF could code for a polypeptide of 312 amino acids (aa) showing 40% homology with the HFV bel1 putative gene product. A more detailed analysis showed that the protein encoded by this ORF would have features characteristic of known trans-activating proteins. The second ORF could code for a polypeptide of 403 aa showing 38% homology with the putative HFV bel2 gene product. Moreover, the 5' extremity of the RNA genome can be folded into a secondary structure identical to the Tat-response element of human immunodeficiency viruses. A phylogenetic tree of retroviruses, including SFV1 and HFV, was constructed. It showed at the molecular level that Spumavirinae, previously classified on the basis of their morphology and their biological properties, constitute a separate group. The homology between SFV1 and HFV reaches 89% in the reverse transcriptase domain of the pol gene. but is much smaller in other parts of the genome.
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PMID:Sequence analysis of the simian foamy virus type 1 genome. 164 58

LP-BM5 murine leukemia virus, a derivative of Duplan-Laterjet virus, contains a mixture of replication-competent B-tropic ecotropic and mink cell focus-inducing (MCF) viruses and a defective genome that is the proximal cause of a syndrome, murine AIDS (MAIDS), characterized by lymphoproliferation and immunodeficiency. The defective (BM5d) and ecotropic components of this mixture were molecularly cloned, and complete (BM5d) or partial (ecotropic) nucleotide sequences were determined. BM5d closely resembled the Du5H genome cloned from the Duplan virus, featuring a highly divergent p12 sequence in the gag open reading frame. In MAIDS-sensitive C57BL/6 mice, BM5d was detected in tissues within 2 weeks of infection but was absent from tissues of the MAIDS-resistant strain, A/J, 12 weeks after infection. B-cell-lineage tumors from mice with MAIDS contained and expressed BM5d, and clonal integrations of this genome were variably associated with clonal expansions of B cells in infected mice. Finally, mRNA crosshybridizing with a probe for BM5d was present in spleen but not kidney cells of uninfected B6 mice.
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PMID:Characteristics and contributions of defective, ecotropic, and mink cell focus-inducing viruses involved in a retrovirus-induced immunodeficiency syndrome of mice. 164 28

cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA.
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PMID:Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation. 165 66

Murine AIDS (MAIDS) is caused by a defective retrovirus which encodes a gag fusion protein (Pr60gag). We previously reported that this virus induced an oligoclonal proliferation of infected cells and suggested that this cell expansion was an important event in the pathogenesis of MAIDS. To identify these target cells, we constructed novel defective viruses whose genomes could be detected with specific probes. Helper-free stocks of these viruses induced MAIDS. Using in situ hybridization and immunocytochemistry and Southern analysis, we found that most infected cells belong to the B-cell lineage. Transformation of these B cells appears to be the primary event responsible for the development of immunodeficiency. This animal model may be relevant to our understanding of AIDS, of the immunodeficiencies associated with B-cell lymphoproliferative disorders, and of the role of B-cell proliferation and transformation in the effects of superantigens, since Pr60gag appears to be a superantigen.
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PMID:The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage. 165 61

We have been studying the role of human cytomegalovirus (HCMV) as a potential cofactor in human immunodeficiency virus (HIV)-related disease. The clinical relevance of HCMV is highlighted by the fact that it is a principal viral pathogen in patients with AIDS and is known to infect the same cells as HIV. In this study, we focused on the molecular interactions between HIV and HCMV in human fibroblasts and in the human glioblastoma/astrocytoma-derived cell line U373 MG, cells which can be productively infected by both viruses. Because these cells are CD4-, we used HIV pseudotyped with a murine amphotropic retrovirus as described previously (D. H. Spector, E. Wade, D. A. Wright, V. Koval, C. Clark, D. Jaquish, and S. A. Spector, J. Virol. 64:2298-2308, 1990). Initial studies showed that when cells were preinfected with HIV (Ampho-1B) for 5 days and then superinfected with HCMV, HIV antigen production dropped significantly in the coinfected cells but continued to rise in cells infected with HIV (Ampho-1B) alone. HCMV production, however, was unaffected by the presence of HIV. Further analysis showed that HIV steady-state RNA levels and gag and env protein production were also inhibited in the presence of HCMV. The transcriptional inhibition of HIV was particularly surprising in view of the previous results of several other laboratories as well as our own that HCMV infection stimulates HIV long terminal repeat-chloramphenicol acetyltransferase (LTR-CAT) expression in transient expression assays. To investigate this further, we transfected the HIV LTR-CAT construct into either uninfected cells or cells which had been preinfected with HIV. The cells were infected with HCMV 24 h posttransfection and assayed for CAT gene expression at 48 h after HCMV infection. Although there was some stimulation of the LTR-CAT in cells that were dually infected by HIV and HCMV, it was 16-fold less than that in the cells infected only with HCMV. This suggests that in the presence of the HIV infection, the stimulation of the HIV LTR-CAT gene by HCMV is significantly reduced. Experiments with UV-irradiated HCMV and the HCMV DNA polymerase inhibitor ganciclovir showed that HCMV transcription is necessary for the reduction in HIV production to occur; however, replication of the HCMV genome or any events which take place after DNA replication are not necessary. These results, coupled with the observation that inhibition is usually first seen between 8 and 24 h after HCMV infection, suggest that an HCMV early protein is involved in repression of HIV.
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PMID:Human cytomegalovirus inhibits human immunodeficiency virus replication in cells productively infected by both viruses. 165 86

RNA pseudoknot structural motifs could have implications for a wide range of biological processes of RNAs. In this study, the potential RNA pseudoknots just downstream from the known and suspected retroviral frame-shift sites were predicted in the Rous sarcoma virus, primate immunodeficiency viruses (HIV-1, HIV-2, and SIV), equine infectious anemia virus, visna virus, bovine leukemia virus, human T-cell leukemia virus (types I and II), mouse mammary tumor virus, Mason-Pfizer monkey virus, and simian SRV-1 type-D retrovirus. Also, the putative RNA pseudoknots were detected in the gag-pol overlaps of two retrotransposons of Drosophila, 17.6 and gypsy, and the mouse intracisternal A particle. For each sequence, the thermodynamic stability and statistical significance of the secondary structure involved in the predicted tertiary structure were assessed and compared. Our results show that the stem-loop structures in the pseudoknots are both thermodynamically highly stable and statistically significant relative to other such configurations that potentially occur in the gag-pol or gag-pro and pro-pol junction domains of these viruses (300 nucleotides upstream and downstream from the possible frameshift sites are included). Moreover, the structural features of the predicted pseudoknots following the frameshift site of pro-pol overlaps of the HTLV-1 and HTLV-2 retroviruses are structurally well conserved. The occurrence of eight compensatory base changes in the tertiary interaction of the two related sequences allow the conservation of their tertiary structures in spite of the sequence divergence. The results support the possible control mechanism for frameshifting proposed by Brierley et al. and Jacks et al.
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PMID:RNA pseudoknots downstream of the frameshift sites of retroviruses. 166 82

Recombinant fowlpox viruses (FPV) containing the env or gag-pol genes of simian immunodeficiency virus from macaques (SIVmac) were constructed. The env, gag, and pol-encoded polypeptides were efficiently expressed and processed in avian cells productively infected with FPV as well as in mammalian cells, in which FPV infection is abortive. In addition, the recombinant FPV expressing the gag-pol genes directed the formation of defective, lentivirus-like particles which were released into the culture medium of infected cells. Coinfection of cells with the env and gag-pol recombinant viruses resulted in the generation of particles containing SIVmac envelope glycoprotein. The applications of this system to vaccine development are discussed.
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PMID:Formation of lentivirus particles by mammalian cells infected with recombinant fowlpox virus. 166 77

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

HIV-1 and HIV-2 both cause AIDS in humans. Simian immunodeficiency viruses (SIV) are non-human primate lentiviruses and the closest known relatives of the HIVs. They closely parallel HIVs in genomic organization and biologic properties. The authors discuss the known HIVs and SIVs of African origin and describe the variability which exists in the different groups. HIV-1 and HIV-2 share approximately 55-60% amino-acid homology in gag and pol, the genes most highly conserved among related retroviruses. HIV-1 is spread widely throughout the world, while HIV-2 infection appears to be concentrated in West Africa. Rare cases of HIV-2 infection have, however, been identified in Europe and America, usually in individuals connected with West Africa. The authors discuss viral genetic variation and variation of biological phenotype, and findings on HIV-1 and HIV-2 from Zaire, Uganda, Cameroon, Tanzania, Ethiopia, Congo, Ghana, the Gambia, Guinea-Bissau, and Cote d'Ivoire.
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PMID:Variability among HIV and SIV strains of African origin. 166 22


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