Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) infection was studied in two different human neuroblastoma cell lines, SK-N-MC and SH-SY5Y. Results from immunofluorescence analysis indicate that SK-N-MC cells express a 68K neurofilament, and SH-SY5Y cells express additionally a 160K to 200K neurofilament complex and thus represent a more differentiated state. HIV-1 infection in these cell lines was demonstrated by nested polymerase chain reaction and further characterized by in situ hybridization, which showed that about 50% of SK-N-MC cells and 20% of SH-SY5Y cells were infected by HIV-1 and contained integrated proviral HIV-1 DNA. Among the cytokines and growth factors studied, tumour necrosis factor alpha (TNF-alpha) enhanced virus production in both cell lines, but to a differing extent, according to our mRNA and p24 antigen capture assay. In SK-N-MC cells the enhancement of HIV-1 mRNA was detected after 24 h of stimulation, and declined to the control level by 48 h. In SH-SY5Y cells a clear-cut stimulation was seen at both time points. By contrast, interleukin-6 (IL-6) enhanced the virus replication only in SK-N-MC cells, as shown at the mRNA level. Immunochemical staining showed no differences in the proportion of HIV-1-positive cells after 48 h of stimulation by TNF-alpha or IL-6 when compared to the control cells. In addition, based on a thymidine incorporation assay, TNF-alpha inhibited, but IL-6 strongly increased, the DNA synthesis in SK-N-MC cells, whereas in the SH-SY5Y cell line no such differences were seen. We discuss the possibility that developing, less-differentiated neurons may be more readily infected by HIV-1 than fully differentiated neurons, and that cytokines such as TNF-alpha and IL-6, which are elevated in HIV-1-infected individuals, may enhance HIV production.
J Gen Virol 1992 Jul
PMID:Activation of integrated human immunodeficiency virus type 1 in human neuroblastoma cells by the cytokines tumour necrosis factor alpha and interleukin-6. 162

The structures of two vaccinia virus genes (B15R and B18R) from near the right inverted terminal repeat are described. These genes encode proteins of 36.5K and 40.7K, respectively, which have an N-terminal hydrophobic sequence, possible sites for attachment of N-linked carbohydrate and a short string of hydrophobic residues near the C terminus. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons established that the two gene products are related to each other (20% identity) and to the immunoglobulin (Ig) superfamily. Intriguingly, the nearest homologues of these proteins in the SWISS-PROT (version 14) database are the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. The product of one of these genes is known to be expressed on the cell surface early during infection and immunity directed against it confer resistance to virus infection without directly neutralizing virus infectivity. We propose a novel method for virus immune evasion in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6 and prevent these cytokines reaching their natural receptors. In consequence the inflammatory response would be diminished and virus replication enhanced.
J Gen Virol 1991 Mar
PMID:Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily. 182 22

The data are presented on the cloning and sequencing of cDNA coding for human interleukin-6. The variability of cDNA proIL-6 cloned from different cellular sources was studied. The variability of cDNA proIL-6 may be expressed as heterogeneity of 5'- and 3'-end sequences of cDNA as well as single base-pair changes.
Mol Gen Mikrobiol Virusol 1991 May
PMID:[Molecular cloning of cDNA encoding human prointerleukin-6]. 189 55

The replication genes (rep) of the virulence plasmid pYVe439-80 of Yersinia enterocolitica were localized and characterized by restriction endonuclease analysis. Comparison with pIB1, a virulence plasmid of Y. pseudotuberculosis, indicates that while the plasmids carry homologous rep genes their location with respect to the highly conserved 'calcium region' is different. This replication function is thermosensitive. Mini-derivatives of pYVe439-80 appear to be rather unstable. The region of pYVe439-80 containing homology to the incD determinant of F was shown to contain a plasmid-stabilization system (par). The region encoding par was characterized by restriction endonuclease analysis. pIB1 contained an homologous par region but located differently. The pYV plasmids thus underwent rearrangements during their divergent evolution. While the positions of rep and par in the two plasmids are inverted with respect to the surrounding loci, our determination of the orientation of each locus rules out the hypothesis of a simple inversion of a quadrant of pYV. The gene encoding YOP5, a 26 kDa protein encoded by pIB1, was cloned on a mobilizable vector and introduced in Y. enterocolitica W22708 containing pYVe227 (indistinguishable from pYVe439-80), mutated in the homologous gene. The recombinant Y. enterocolitica secreted YOP5. Hence, the transcriptional activation and secretion systems of pYVe227 act on a yop gene from pIB1 and on its product, indicating that these systems are interchangeable.
J Gen Microbiol 1988 Jun
PMID:The replication, partition and yop regulation of the pYV plasmids are highly conserved in Yersinia enterocolitica and Y. pseudotuberculosis. 322 Nov 96

Monocyte-derived macrophages (MDM) were demonstrated to be susceptible to productive infection by the monocytotropic human immunodeficiency virus type 1 (HIV-1) strain HIV-1/Ba-L and by three primary HIV-1 isolates, HIV-1/DAS, HIV-1/PAR and HIV-1/THI. Production of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-1 beta was monitored between days 3 and 26 after MDM infection. TNF-alpha and IL-6 were detected in cell culture supernatants from days 16 to 21 following HIV-1/DAS, HIV-1/PAR and HIV-1/Ba-L infection, at the time of high viral replication. IL-1 beta was not found at the same time points. TNF-alpha mRNA expression occurred around the peak of both TNF-alpha levels and supernatant RT activities. In HIV-1/THI-infected macrophage cultures no endogenously produced TNF-alpha was observed, despite high levels of HIV-1 in MDM. This result demonstrates that a primary isolate may replicate independently of TNF-alpha in MDM. To investigate the relationship between TNF-alpha and viral replication we used a TNF-alpha synthesis inhibitor, RP 55778. Treatment throughout the course of cell culture resulted in a significant decrease in both TNF-alpha levels and viral production in HIV-1/DAS-, HIV-1/PAR- and HIV-1/Ba-L-infected MDM cultures. This phenomenon is reversed by adding recombinant human TNF-alpha to the RP 55778-treated cell cultures from day 14 post-infection. No effect of RP 55778 was observed in MDM cultures infected with the primary isolate HIV-1/THI, whose replication is independent of TNF-alpha production and therefore remained unchanged after RP 55778 treatment. We conclude that the clinical value of such a drug is directly dependent on the ability of the HIV-1 strains involved to induce TNF-alpha production at the time of viral replication.
J Gen Virol 1994 Jun
PMID:Infection of human macrophages with an endogenous tumour necrosis factor-alpha (TNF-alpha)-independent human immunodeficiency virus type 1 isolate is unresponsive to the TNF-alpha synthesis inhibitor RP 55778. 751 38

An animal model of chronic enteroviral infection was established by using PCR to detect viral genomes in animal tissues and to compare levels of transcription of a variety of cytokines in the brain. Chronic coxsackie-virus B1 infection was found in both brain and skeletal muscle of mice infected as neonates. The viral infection cleared by 240 days post-infection. Elevated levels of tumour necrosis factor alpha and interleukin-6 (IL-6) would appear to be linked to acute and chronic infection respectively. Levels of IL-6 return to normal upon clearance of the virus.
J Gen Virol 1993 Apr
PMID:Increased transcription of interleukin-6 in the brains of mice with chronic enterovirus infection. 838 99

Since modulation of the glutathione (GSH) level has been implicated in the regulation of human immunodeficiency virus (HIV) transcription and expression, we have undertaken an analysis of the effect of sodium valproate (VPA) on HIV-1 replication. VPA, which is an anti-epileptic drug in widespread use in clinical medicine, has been shown to depress the activity of GSH reductase, an enzyme required for maintaining high cellular levels of reduced GSH. The effect of this drug on HIV-1 replication has been studied in primary infected cells, i.e. peripheral blood mononuclear cells (PBMC) and monocyte/macrophages, in the CEM-SS cell line, and in chronically infected stimulated and non-stimulated U1 cells. We have shown that VPA markedly enhanced viral replication in all infected cells tested. Virus production was induced in U1 cells by VPA treatment and the stimulatory effects of tumour necrosis factor-alpha, interleukin-6 and granulocyte/macrophage colony-stimulating factor were augmented. The LTR-driven gene expression in Jurkat T cells was increased. However, the elevated viral production did not correlate with the effect of VPA on the intracellular GSH level. Thus, VPA stimulated in vitro HIV-1 replication in acutely and chronically infected cells and enhanced LTR-driven gene expression. These effects were observed for concentrations that are reached in the plasma of VPA-treated patients. Therefore, although the clinical significance of these data remains to be demonstrated, these results should be considered in the choice of an anticonvulsant drug in HIV-infected individuals.
J Gen Virol 1996 Sep
PMID:Sodium valproate, an anticonvulsant drug, stimulates human immunodeficiency virus type 1 replication independently of glutathione levels. 881 Sep 95

The complete sequence of the single-stranded, (+)-sense RNA genome of saguaro cactus carmovirus (SCV) has been determined. The 3879 nucleotide genome contains five open reading frames (ORFs). The 5'-proximal ORF encodes a 26 kDa protein (p26) and terminates with an amber codon which is readthrough into an in-frame p57 ORF to generate an 86 kDa fusion protein (p86). Two small, centrally located ORFs encode a 6 kDa protein (p6) and a 9 kDa protein (p9), respectively. The 3'-proximal ORF encodes a 37 kDa (p37) capsid protein (CP). Analysis of the nucleotide and predicted amino acid sequences supports the classification of SCV in the genus Carmovirus in the family Tombusviridae. All predicted SCV proteins are expressed in an in vitro translation system. SCV p26 and the readthrough fusion protein p86 are synthesized from the genomic RNA while p6, p9 and p37 CP ORFs at the 3' half of the genome are expressed from two subgenomic (sg) RNAs. The 5' termini of both sg RNAs have been mapped. The large 1614 nucleotide sg RNA contains the p6 and p9 ORFs as the first and the second ORFs respectively from its 5' end. It directs the synthesis of abundant p6 but a small amount of p9. While a synthetic transcript with the p9 ORF at the 5' end is a more efficient messenger for p9, no corresponding sg RNA has been identified in vivo. The smaller 1396 nucleotide sg RNA contains only the p37 ORF and directs the synthesis of SCV CP.
J Gen Virol 1997 Mar
PMID:Genome organization and gene expression of saguaro cactus carmovirus. 904

During immunodeficiency after sublethal haematoablative treatment, cytomegalovirus (CMV) infection interferes with haematopoietic reconstitution and can cause lethal bone marrow (BM) aplasia. The in vivo model of murine CMV infection has identified the BM stroma as the principal target site of CMV in the haematopoietic cord. The infected cell type is the reticular stromal cell which forms the stromal network and produces essential haemopoietins, such as stem-cell factor (SCF). The expression of SCF was found to be reduced in the infected stroma, but the stromal network was not disrupted and the number of infected stromal cells was too low to explain the functional deficiency. These facts call for a negatively regulating cytokine that is induced by the infection and that potentiates the direct effect of infection by down-regulating haemopoietins in uninfected bystander cells. Recent work has suggested that transforming growth factor (TGF)-beta1 might be the cytokine involved in CMV-induced BM aplasia. We show here that murine CMV indirectly induces the accumulation of mature TGF-beta1 in uninfected renal tubular epithelial cells and TGF-beta1 transcription in BM stromal cells, whereas infected renal glomerular and interstitial cells, hepatocytes and BM stromal cells do not coexpress mature TGF-beta1. Antiviral CD8 T-cell therapy prevented BM aplasia and also prevented the down-regulation of stromal SCF and interleukin-6 gene expression. Interestingly, however, the CD8 T cells did not preclude the up-regulation of mature TGF-beta1, but proved to be inducers of TGF-beta1 gene expression in BM stroma. These findings suggest that TGF-beta1 is not the mediator of BM aplasia.
J Gen Virol 1998 Apr
PMID:Evidence against a key role for transforming growth factor-beta1 in cytomegalovirus-induced bone marrow aplasia. 956 83

Retroperitoneal fibromatosis-associated herpesvirus of rhesus macaques (RFHVMm) is a gammaherpesvirus closely related to human herpesvirus-8 (HHV-8), which is thought to be a necessary cofactor for the development of Kaposi's sarcoma (KS) in humans. Here, RFHVMm infection of rhesus macaques exposed to the D-type retrovirus simian retrovirus-2 (SRV-2) is described. Development of SRV-2 viraemia, infection with simian immunodeficiency virus or administration of cyclosporin A could result in persistent RFHVMm viraemia. From this, it is concluded that productive retrovirus infection or otherwise-induced immune suppression has the ability to activate this herpesvirus in vivo. Elevated levels of circulating interleukin-6, a cytokine that plays a central role in KS, were found in RFHVMm-viraemic animals. In viraemic animals, RFHVMm was found in tissues that are common sites for the development of AIDS-associated KS, especially the oral cavity. Together, these data suggest a common biology between RFHVMm infection of macaques and HHV-8 infection and pathogenesis in humans.
J Gen Virol 1999 Feb
PMID:Activation in vivo of retroperitoneal fibromatosis-associated herpesvirus, a simian homologue of human herpesvirus-8. 1007 9


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