Plasminogen Controls Inflammation and Pathogenesis of Influenza Virus Infections via Fibrinolysis

Berri, Fatma; Rimmelzwaan, Guus F.; Hanss, Michel; Albina, Emmanuel; Foucault-Grunenwald, Marie-Laure; Lê, Vuong Ba; Trierum, Stella E. Vogelzang-van; Gil, Patricia; Camerer, Eric; Martinez, Dominique; Lina, Bruno; Lijnen, Roger; Carmeliet, Peter; Riteau, Béatrice

doi:10.1371/journal.ppat.1003229

Cited by 79 publications

(74 citation statements)

References 47 publications

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“…In line with our observations, a reduction of fibrinogen levels with the snake venom ancrod also increased the severity of IAV infection in mice. 88 Taken together, these results suggest that antithrombotic therapy may have an adverse effect during IAV infection by increasing lung hemorrhages and mortality.…”

Section: Roles Of the Coagulation Cascade And Platelets In Mouse Modementioning

confidence: 82%

Multiple roles of the coagulation protease cascade during virus infection

Antoniak

Mackman

2014

Blood

192

205

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The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

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Section: Roles Of the Coagulation Cascade And Platelets In Mouse Modementioning

confidence: 82%

Multiple roles of the coagulation protease cascade during virus infection

Antoniak

Mackman

2014

Blood

192

205

View full text Add to dashboard Cite

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“…Furthermore, IL-1 plays an important role in hemostasis deregulation through tissue factor induction. Since hemostasis deregulation emerges as a key pathway in cytokine storm induced by influenza viruses [3,4,18], it seems reasonable to speculate that human signature residues in the M2 protein of AIVs may be involved in cytokine storm via IL-1 production and hemostasis deregulation.…”

Section: Discussionmentioning

confidence: 99%

“…This is despite the fact that the past documented pandemics (i.e. 1918 H1N1, 1957 H2N2, 1968 H3N2 and 2009 H1N1) were caused by viruses of non-highly pathogenic subtypes 4 and possessed some genes of avian origin. Moreover, the recent pandemic threat due to a novel reassortant avian-origin influenza A (H7N9) virus found in China is of low pathogenic pathotype [12].…”

Section: Introductionmentioning

confidence: 98%

The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia

et al. 2014

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Whilst remarkable progress in elucidating the mechanisms governing interspecies transmission and pathogenicity of highly pathogenic avian influenza viruses (AIVs) have been made, similar studies focusing on low pathogenic AIVs isolated from the wild waterfowl reservoir are limited.We previously reported that two AIV strains (subtypes H6N2 and H3N8) isolated from wild waterfowl in Zambia harbored some amino acid residues preferentially associated with human influenza virus proteins (so-called human signatures) and replicated better in the lungs of infected mice and caused more morbidity than a strain lacking such residues. To further substantiate these observations, we infected chickens and mice intranasally with AIV strains of various subtypes (H3N6, H3N8, H4N6, H6N2, H9N1 and H11N9) isolated from wild waterfowl in Zambia. Although some strains induced seroconversion, all the tested strains replicated poorly and were nonpathogenic for chickens. In contrast, most of the strains having human signatures replicated well in the lungs of mice, and one of these strains caused severe illness in mice and induced lung injury that was characterized by a severe accumulation of polymorphonuclear leukocytes. These results suggest that some strains tested in this study may have the potential to directly infect mammalian hosts without adaptation, which might possibly be associated with the possession of human signature residues. Close monitoring and evaluation of host-associated signatures may help elucidate the prevalence and emergence of AIVs with potential of causing zoonotic infections.

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“…Plasmin and fibrin are activated serine proteases that increase during influenza possibly activating viral hemagglutinin, and serve as markers of inflammation. 12 It is known that the viral hemagglutinin binds plasminogen which may have a role in its activation and infection of pulmonary cells. 13 A molecular mechanism explaining synergistic mortality during simultaneous malaria and influenza infections therefore may be the cooperative interaction of parasite and host proteins, which may exaggerate pulmonary infection and inflammation.…”

mentioning

confidence: 99%

“…13 A molecular mechanism explaining synergistic mortality during simultaneous malaria and influenza infections therefore may be the cooperative interaction of parasite and host proteins, which may exaggerate pulmonary infection and inflammation. 12 Such inflammation may have increased pulmonary failure or led to ineffective host response to secondary bacterial pneumonias that appear to have been the proximate cause of death of most victims of the 1918 influenza pandemic.…”

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confidence: 99%

Synergistic Mortality Caused by Plasmodium falciparum During the 1918 Influenza Pandemic

Shanks¹

2015

The American Society of Tropical Medicine and Hygiene

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Abstract. At the end of World War I, British medical officers noted that soldiers infected with malaria were more likely to die during the 1918 influenza pandemic than those without malaria. This synergistic mortality appeared to be specific to Plasmodium falciparum and has not been generally noted since 1920. A possible explanation is that a malariainduced procoagulant state enhanced the activation of influenza virus to increase inflammation and subsequent severe clinical outcomes. Falciparum proteins bind and likely inhibit antithrombin 3 and other factors. Pathogens interact in ways that may inform pathophysiology studies of remote epidemics.The co-existence of a malarial infection seemed to render the patient extremely susceptible to this post-influenzal pneumonia and to lower his chance of recovery from it almost to vanishing point. (W Angus, Palestine 1919) 1 The influenza pandemic of 1918 killed more people than died during World War I.2 Although influenza pandemics have reappeared intermittently, the extreme mortality of influenza in 1918-1920 has never been well explained, especially its unique concentration in young adults from 20 to 40 years of age.3 During World War I, British Army soldiers were severely affected by malaria in Palestine (modern Israel/Jordan/Syria), Macedonia (modern Greece), and Mesopotamia (modern Iraq). When the influenza pandemic arrived at the end of the war, severe clinical outcomes were observed nearly everywhere, but some of the highest mortality rates were in soldiers simultaneously infected with falciparum malaria. Although limited by the laboratory resources available in that era, keen clinical observers detected synergistic mortality between falciparum malaria and pandemic influenza in all the three countries and confirmed their findings with postmortem studies. [4][5][6] That the two pathogens might increase mortality when they simultaneously infected the same person was not surprising, but the independently reported mortality of dually infected soldiers was so great as to raise questions regarding the pathophysiology especially because this effect has not been observed since 1920. Insight may be obtained by constructing plausible scenarios based on modern understanding of infection and inflammation specifically Plasmodium falciparum's effect on the coagulation cascade. An interaction between parasite and viral proteins is hypothesized to be a likely explanation of synergistic mortality during the influenza pandemic of 1918.The increased mortality of combined influenza and malaria infections was spontaneously noted by the medical officers in 1918 despite the very different military and public health situations in Palestine, Macedonia, and Mesopotamia. [4][5][6] Postmortem studies in Palestine by Fairley showed 59% of 80 malaria deaths complicated by influenza, in Egypt MansonBahr observed 48% of 67 malaria deaths complicated by influenza and in Macedonia out of 100 deaths due to influenza, 83% also had malaria infection. [4][5][6] The massive number of casualties occurri...

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Plasminogen Controls Inflammation and Pathogenesis of Influenza Virus Infections via Fibrinolysis

Cited by 79 publications

References 47 publications

Multiple roles of the coagulation protease cascade during virus infection

Multiple roles of the coagulation protease cascade during virus infection

The zoonotic potential of avian influenza viruses isolated from wild waterfowl in Zambia

Synergistic Mortality Caused by Plasmodium falciparum During the 1918 Influenza Pandemic

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