Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies attempt to understand more fully the host response and pathogenesis associated with severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) by monitoring gene expression using formalin-fixed paraffin-embedded (FFPE) pulmonary autopsy tissues. These tissues were from patients in different hospitals in Singapore who were diagnosed with various microbial infections, including SARS-CoV, that caused acute respiratory distress syndrome (ARDS). Global expression patterns showed limited correlation between end-stage ARDS and the initiating pathogen, but when focusing on a subset of genes implicated in pulmonary pathogenesis, molecular signatures of pulmonary disease were obtained and appeared to be influenced by preexisting pulmonary complications and also bacterial components of infection. Many factors detected during pulmonary damage and repair, such as extracellular matrix (ECM) components, transforming growth factor (TGF) enhancers, acute-phase proteins, and antioxidants, were included in the molecular profiles of these ARDS lung tissues. In addition, differential expression of cytokines within these pulmonary tissues were observed, including notable genes involved in the interferon (IFN) pathway, such as Stat1, IFN regulatory factor-1 (IRF-1), interleukin-6 (IL-6), IL-8, and IL-18, that are often characterized as elevated in ARDS patients.
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PMID:SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues. 1668 59

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.
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PMID:Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation. 1714 Dec 29

Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in approximately 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models.
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PMID:The Immunobiology of SARS*. 1724 93

The clinical picture of severe acute respiratory syndrome (SARS) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. To understand how cells response in the early stage of virus-host cell interaction, in this study, a purified recombinant S protein was studied for stimulating murine macrophages (RAW264.7) to produce proinflammatory cytokines (IL-6 and TNF-alpha) and chemokine IL-8. We found that direct induction of IL-6 and TNF-alpha release in the supernatant in a dose-, time-dependent manner and highly spike protein-specific, but no induction of IL-8 was detected. Further experiments showed that IL-6 and TNF-alpha production were dependent on NF-kappaB, which was activated through I-kappaBalpha degradation. These results suggest that SARS-CoV spike protein may play an important role in the pathogenesis of SARS, especially in inflammation and high fever.
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PMID:Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. 1753 82

Murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS) coronavirus (CoV) are two of the best-studied representatives of the family Coronaviridae. During CoV infection, numerous cytokines and chemokines are induced in vitro and in vivo. Human interleukin 8 and its mouse functional counterpart, CXCL2, are early-expressed chemokines. Here we show that SARS-CoV and MHV induce endoplasmic reticulum (ER) stress and Cxcl2 mRNA transcription during infection in vitro. Expression of the viral spike protein significantly induced ER stress and Cxcl2 mRNA upregulation, while expression of the other structural genes did not. Additional experiments with UV-inactivated virus, cell-cell fusion-blocking antibodies, and an MHV mutant with a defect in spike protein maturation demonstrated that spike-host interactions in the ER are responsible for the induction of ER stress and subsequent Cxcl2 mRNA transcription. Despite significant increases in levels of Cxcl2 mRNA and functional nucleus-to-cytoplasm RNA transport, no CXCL2 protein was released into the medium from MHV-infected cells. Yet Sendai virus-infected cells showed substantial Cxcl2 mRNA induction and a simultaneous increase in levels of secreted CXCL2 protein. Our results demonstrate that expression of CoV spike proteins induces ER stress, which could subsequently trigger innate immune responses. However, at that point in infection, translation of host mRNA is already severely reduced in infected cells, preventing the synthesis of CXCL2 and ER stress proteins despite their increased mRNA concentrations.
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PMID:The coronavirus spike protein induces endoplasmic reticulum stress and upregulation of intracellular chemokine mRNA concentrations. 1767 Aug 39

The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis) that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL)-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs) and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.
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PMID:Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques. 1769 9

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes SARS. The pathogenic mechanisms of SARS-CoV remain poorly understood. Six cynomolgus monkeys were inoculated with the HKU39849 isolate of SARS-CoV via four routes. After intranasal inoculation, the virus was isolated from respiratory swabs on days 2-7 postinoculation (p.i.) and virus genome was detected in intestinal tissues on day 7 p.i. Virus was not detected after intragastric inoculation. After intravenous inoculation, infectious virus was isolated from rectal swabs, and virus antigen was detected in intestinal cells on day 14 p.i. After intratracheal (i.t.) inoculation, virus antigen-positive alveolar cells and macrophages were found in lung and infectious virus was detected in lymphoid and intestinal tissues. The peribronchial lymph nodes showed evidence of an immune response. Lung tissue and/or fluid and/or the peribronchial lymph node of the intratracheally inoculated animals had high TNF-alpha, IL-8 and IL-12 levels. SARS lung lesions are only generated in monkeys by i.t. inoculation. The virus appears to spread into and perhaps via the intestinal and lymphatic systems. It has been suggested previously that viraemia may cause intestinal infections in SARS patients.
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PMID:Pathology and virus dispersion in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus via different inoculation routes. 1803 77

In response to viral infection, the expression of numerous host genes, including predominantly a number of proinflammatory cytokines and chemokines, is usually up-regulated at both transcriptional and translational levels. It was noted that in cells infected with coronavirus, transcription and translation of some of these genes were differentially induced. Drastic induction of their expression at the transcriptional level was observed in cells infected with coronavirus. However, induction of the same genes at the translational level was usually found to be minimal to moderate. To investigate the underlying mechanisms, yeast two-hybrid screen was carried out using SARS-CoV proteins as baits, revealing that a subunit of the eukaryotic initiation factor 3 (eIF3), eIF3f, may interact with the N-terminal region of the SARS-CoV spike (S) protein. This interaction was subsequently confirmed by co-immunoprecipitation and immunofluorescent staining. Meanwhile, parallel experiments confirmed that eIF3f could also interact with the S protein of another coronavirus, the avian coronavirus infectious bronchitis virus (IBV). These interactions led to the inhibition of translation of a reporter gene in both in vitro expression system and intact cells. Interestingly, IBV-infected cells stably expressing a Flag-tagged eIF3f showed much higher translation of IL-6 and IL-8, suggesting that the interaction between coronavirus S protein and eIF3f plays a functional role in controlling the expression of host genes, especially genes that are induced during coronavirus infection cycles. This study reveals a novel mechanism exploited by coronavirus to regulate viral pathogenesis.
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PMID:Coronavirus spike protein inhibits host cell translation by interaction with eIF3f. 1823 81

Molecular mimicry, defined as similar structures shared by molecules from dissimilar genes or proteins, is a general strategy used by pathogens to infect host cells. Severe acute respiratory syndrome (SARS) is a new human respiratory infectious disease caused by SARS coronavirus (SARS-CoV). The spike (S) protein of SARS-CoV plays an important role in the virus entry into a cell. In this study, eleven synthetic peptides from the S protein were selected based on its sequence homology with human proteins. Two of the peptides D07 (residues 927-937) and D08 (residues 942-951) were recognized by the sera of SARS patients. Murine hyperimmune sera against these peptides bound to proteins of human lung epithelial cells A549. Another peptide D10 (residues 490-502) stimulated A549 to proliferate and secrete IL-8. The present results suggest that the selected S protein regions, which share sequence homology with human proteins, may play important roles in SARS-CoV infection.
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PMID:Peptide mimicrying between SARS coronavirus spike protein and human proteins reacts with SARS patient serum. 1832 19

The sudden emergence of severe acute respiratory syndrome (SARS) has boosted research on innate immune responses to coronaviruses. It is now well established that the causative agent, a newly identified coronavirus termed SARS-CoV, employs multiple passive and active mechanisms to avoid induction of the antiviral type I interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are strongly upregulated. The imbalance in the IFN response is thought to contribute to the establishment of viremia early in infection, whereas the production of chemokines by infected organs may be responsible for (i) massive immune cell infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of adaptive immunity. Here, we will review the most recent findings on the interaction of SARS-CoV and related Coronaviridae members with the type I interferon and cytokine responses and discuss implications for pathogenesis and therapy.
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PMID:Interferon and cytokine responses to SARS-coronavirus infection. 1832 65


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