Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fourteen cytokines or chemokines were analyzed on 88 RT-PCR-confirmed severe acute respiratory syndrome (SARS) patients. IFN-gamma, IL-18, TGF-beta, IL-6, IP-10, MCP-1, MIG, and IL-8, but not of TNF-alpha, IL-2, IL-4, IL-10, IL-13, or TNFRI, were highly elevated in the acute phase sera of Taiwan SARS patients. IFN-gamma was significantly higher in the Ab(+) group than in the Ab(-) group. IFN-gamma, IL-18, MCP-1, MIG, and IP-10 were already elevated at early days post fever onset. Furthermore, levels of IL-18, IP-10, MIG, and MCP-1 were significantly higher in the death group than in the survival group. For the survival group, IFN-gamma and MCP-1 were inversely associated with circulating lymphocytes count and monocytes count, but positively associated with circulating neutrophils count. It is concluded that an interferon-gamma-related cytokine storm was induced post SARS coronavirus infection, and this cytokine storm might be involved in the immunopathological damage in SARS patients.
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PMID:An interferon-gamma-related cytokine storm in SARS patients. 1560 37

Lymphopenia and increasing viral load in the first 10 days of severe acute respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV). In this study, we focused on dendritic cells (DCs) which play important roles in linking the innate and adaptive immunity. SARS-CoV was shown to infect both immature and mature human monocyte-derived DCs by electron microscopy and immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs suggested viral replication. However, no increase in viral RNA was observed. Using cytopathic assays, no increase in virus titer was detected in infected DCs and cell-culture supernatant, confirming that virus replication was incomplete. No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs. The SARS-CoV-infected DCs showed low expression of antiviral cytokines (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL-12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on activation normal T cell expressed and secreted [RANTES]), interferon-inducible protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The lack of antiviral cytokine response against a background of intense chemokine up-regulation could represent a mechanism of immune evasion by SARS-CoV.
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PMID:Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. 1586 Jun 69

The authors have previously shown that acute lung injury (ALI) produces a wide spectrum of pathological processes in patients who die of severe acute respiratory syndrome (SARS) and that the SARS coronavirus (SARS-CoV) nucleoprotein is detectable in the lungs, and other organs and tissues, in these patients. In the present study, immunohistochemistry (IHC) and in situ hybridization (ISH) assays were used to analyse the expression of angiotensin-converting enzyme 2 (ACE2), SARS-CoV spike (S) protein, and some pro-inflammatory cytokines (PICs) including MCP-1, TGF-beta1, TNF-alpha, IL-1beta, and IL-6 in autopsy tissues from four patients who died of SARS. SARS-CoV S protein and its RNA were only detected in ACE2+ cells in the lungs and other organs, indicating that ACE2-expressing cells are the primary targets for SARS-CoV infection in vivo in humans. High levels of PICs were expressed in the SARS-CoV-infected ACE2+ cells, but not in the uninfected cells. These results suggest that cells infected by SARS-CoV produce elevated levels of PICs which may cause immuno-mediated damage to the lungs and other organs, resulting in ALI and, subsequently, multi-organ dysfunction. Therefore application of PIC antagonists may reduce the severity and mortality of SARS.
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PMID:Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. 1703 79

Severe acute respiratory syndrome (SARS) is a life-threatening infectious disease which has been difficult to study and treat because of the lack of a readily available animal model. Intranasal infection of A/J mice with the coronavirus murine hepatitis virus strain 1 (MHV-1) produced pulmonary pathological features of SARS. All MHV-1-infected A/J mice developed progressive interstitial pneumonitis, including dense macrophage infiltrates, giant cells, and hyaline membranes, resulting in death of all animals. In contrast, other mouse strains developed only mild transitory disease. Infected A/J mice had significantly higher cytokine levels, particularly macrophage chemoattractant protein 1 (MCP-1/CCL-2), gamma interferon, and tumor necrosis factor alpha. Furthermore, FGL2/fibroleukin mRNA transcripts and protein and fibrin deposits were markedly increased in the lungs of infected A/J mice. These animals developed a less robust type I interferon response to MHV-1 infection than resistant C57BL/6J mice, and treatment with recombinant beta interferon improved survival. This study describes a potentially useful small animal model of human SARS, defines its pathogenesis, and suggests treatment strategies.
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PMID:Murine hepatitis virus strain 1 produces a clinically relevant model of severe acute respiratory syndrome in A/J mice. 1704 Dec 19

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

Coinfection with two or more pathogens is a common occurrence in respiratory diseases of most species. The manner in which multiple pathogens interact is not always straightforward, however. Bordetella bronchiseptica and porcine respiratory coronavirus (PRCV) are respiratory pathogens of pigs whose relatives, B. pertussis and the SARS virus, cause respiratory disease in humans. In an initial experiment, the effect of coinfection of PRCV and B. bronchiseptica was examined in thirty, 4-week-old pigs (10 pigs/group) that were infected with either PRCV or B. bronchiseptica, or both PRCV and B. bronchiseptica. An additional 10 pigs served as sham infected controls. Five pigs from each group were euthanized at 4 and 10 days post-infection. Gross and histopathological lung lesions were more severe in the coinfected group as compared to the groups infected with B. bronchiseptica or PRCV alone. In order to investigate the potential role of proinflammatory cytokines in disease severity after coinfection, a second experiment was performed to examine cytokine transcription in alveolar macrophages from single and dually infected pigs. A total of 48 pigs were divided equally into groups as above, but 4 pigs from each group were euthanized at 1, 4 and 10 days post-infection. Coinfected pigs showed a greater and more sustained transcription of proinflammatory cytokines, especially IL-6 and MCP-1, than pigs infected with either PRCV or B. bronchiseptica alone. Thus, there appears to be a synergistic effect between PRCV and B. bronchiseptica with regards to proinflammatory cytokine transcription that may partially explain the increased severity of pneumonia in coinfected pigs.
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PMID:Coinfection of pigs with porcine respiratory coronavirus and Bordetella bronchiseptica. 1802 32

1. The IFN-gamma +874A allele and RANTES -28 G allele are risk factors for SARS susceptibility. 2. The RANTES -28 G allele plays a role in the pathogenesis of SARS. 3. The polymorphisms of IL-10, TNF-alpha, IL-12, IP-10, Mig and MCP-1 are not associated with SARS susceptibility.
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PMID:Association of cytokine and chemokine gene polymorphisms with severe acute respiratory syndrome. 1925 35

We evaluated the efficacy of three SARS vaccine candidates in a murine SARS model utilizing low-virulence Pp and SARS-CoV coinfection. Vaccinated mice were protected from severe respiratory disease in parallel with a low virus titer in the lungs and a high neutralizing antibody titer in the plasma. Importantly, the administration of spike protein-specific neutralizing monoclonal antibody protected mice from the disease, indicating that the neutralization is sufficient for protection. Moreover, a high level of IL-6 and MCP-1 production, but not other 18 cytokines tested, on days 2 and 3 after SARS-CoV infection was closely linked to the virus replication and disease severity, suggesting the importance of these cytokines in the lung pathogenicity of SARS-CoV infection.
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PMID:Neutralizing antibody against severe acute respiratory syndrome (SARS)-coronavirus spike is highly effective for the protection of mice in the murine SARS model. 1929 Oct 90

Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5- to 6-week-old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1alpha, IL-6, MIP-1alpha, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhibitors of SARS-CoV replication. In v2163-infected mice, Ampligen was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA, and Ampligen decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.
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PMID:A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. 1985 71

The outbreak of severe acute respiratory syndrome (SARS) in 2003 in China, characterized by atypical pneumonia, was associated with the emergence of a novel coronavirus named severe acute respiratory syndrome coronavirus (SARS-CoV). Eight accessory proteins of SARS coronavirus were the suspected players in the pathogenesis of the virus. Among them, protein 3b localizes to the nucleus and behaves as an interferon antagonist by inhibiting IRF3 activation. However, the effect of 3b on the activity of other common host transcription factors remains unexplored. In this work, we studied the effect of 3b on the transcriptional activity of AP-1. Our findings elucidate augmentation of AP-1-dependent gene expression in 3b-transfected Huh7 cells. Reporter gene and mobility shift assays depict an increase in the AP-1 transcriptional and DNA binding activity in the presence of 3b. This increase in activity correlates with the activation of ERK and JNK pathways. Furthermore, 3b expression potentiates AP-1-driven promoter activity of proinflammatory cytokine MCP-1, suggesting a plausible role for 3b as a virulence factor that might function by upregulating AP-1-dependent cytokine levels in SARS-CoV infection.
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PMID:SARS-CoV accessory protein 3b induces AP-1 transcriptional activity through activation of JNK and ERK pathways. 2156 Oct 61


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