Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

Vogel, A.; Harris, Seth P.; Marsteller, Nathan L.; Condon, Shirley A.; Brown, Deborah M.

doi:10.1089/vim.2013.0095

Cited by 35 publications

(38 citation statements)

References 47 publications

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“…The dysregulation of pro‐inflammatory cytokine production induced by IAV was further confirmed in vivo by infection of mice with IAV. The results are consistent with many other studies that upon the infection of IAV, mice produced dramatically higher levels of TNF‐α, IFN‐α, and IL‐6 . Thus, we aimed to find out an agent to inhibit the inflammatory responses of macrophages and alleviate the acute lung injury induced by IAV infection.…”

Section: Discussionsupporting

confidence: 89%

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

Liu

2017

Influenza Resp Viruses

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BackgroundInfluenza A viruses (IAV) result in severe public health problems with worldwide each year. Overresponse of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality.ObjectiveCurcumin has been reported to have anti‐inflammatory ability. However, its molecular mechanism in immune responses remains unclear.MethodsWe detected the pro‐inflammatory cytokine secretion and nuclear factor kappa‐light‐chain‐enhancer of activated B cell (NF‐κB)‐related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment.ResultsWe found that the IAV infection caused a dramatic enhancement of pro‐inflammatory cytokine productions of human macrophages and mice immune cells. However, curcumin treatment after IAV infection downregulated these cytokines production in a dose‐dependent manner. Moreover, the NF‐κB has been activated in human macrophages after IAV infection, while administration of curcumin inhibited NF‐κB signaling pathway via promoting the expression of nuclear factor of kappa light polypeptide gene enhancer in B‐cells inhibitor, alpha (IκBα), and inhibiting the translocation of p65 from cytoplasm to nucleus.ConclusionsIn summary, IAV infection could result in the inflammatory responses of immune cells, especially macrophages. Curcumin has the therapeutic potentials to relieve these inflammatory responses through inhibiting the NF‐κB signaling pathway.

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Section: Discussionsupporting

confidence: 89%

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

Liu

2017

Influenza Resp Viruses

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“…Multiple studies have shown that inflammation during influenza and other respiratory viral infections can cause pathogenesis that is independent of viral levels in the lungs (42,43,(46)(47)(48). Our histopathology data are in agreement with studies that demonstrate excessive inflammatory responses occurring as viral loads are decreasing (25,49). We inoculated mice with influenza A virus PR8 2 days after RV inoculation, which is just prior to the decline in neutrophil numbers in the lungs of RV-infected BALB/c mice (29).…”

Section: Discussionsupporting

confidence: 89%

“…In order to study the effects of viral coinfection on influenza disease pathogenesis, we established a mouse model of coinfection using mouse-adapted influenza A virus strain A/Puerto Rico/ 8/1934 (PR8). PR8 infection in BALB/c mice causes dose-dependent disease severity, in which mortality corresponds with early viral replication and cytokine production, followed by massive cellular infiltration in the lungs (25)(26)(27). To determine how PR8-mediated disease is altered by a mild viral infection, we coinfected mice with human rhinovirus strain 1B (RV1B) or a murine coronavirus, mouse hepatitis virus strain 1 (MHV-1).…”

mentioning

confidence: 99%

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

González

Ijezie

Balemba

et al. 2018

J Virol

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Influenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other's spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia or Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses. Viral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.

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“…The influenza virus strain A/Puerto Rico/8/34 (H1N1) used in this study is a highly virulent, mouse‐adapted virus, which was prepared as described previously . An A/Puerto Rico/8/34 (H1N1) infection is treatable with NAI …”

Section: Methodsmentioning

confidence: 99%

Combined effect of anti‐high‐mobility group box‐1 monoclonal antibody and peramivir against influenza A virus‐induced pneumonia in mice

Hatayama

Nosaka

Yamada

et al. 2018

Journal of Medical Virology

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Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti‐inflammatory effect of anti‐high‐mobility group box‐1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti‐HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine‐week‐old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post‐infection (dpi). The anti‐HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti‐HMGB1 mAb significantly improved survival rate whereas the anti‐HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti‐HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti‐HMGB1 with conventional anti‐influenza therapy might be useful against severe influenza virus infection.

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Early Cytokine Dysregulation and Viral Replication Are Associated with Mortality During Lethal Influenza Infection

Cited by 35 publications

References 47 publications

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection through inhibiting the NF‐κB signaling pathway

Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

Combined effect of anti‐high‐mobility group box‐1 monoclonal antibody and peramivir against influenza A virus‐induced pneumonia in mice

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