Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus

Kobasa, Darwyn; Jones, Steven M.; Shinya, Kyoko; Kash, John C.; Copps, John; Ebihara, Hideki; Hatta, Yasuko; Kim, Jin Hyun; Halfmann, Peter; Hatta, Masato; Feldmann, Friederike; Alimonti, Judie B.; Fernando, Lisa; Li, Yan; Katze, Michael G.; Feldmann, Heinz; Kawaoka, Yoshihiro

doi:10.1038/nature05495

Cited by 870 publications

(871 citation statements)

References 28 publications

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“…Experimental animal data with both the H5N1 viruses and the 1918 influenza viruses suggest that virulence is polygenic and depends on a complementary relationship among viral gene segments. [13][14] In mammals, H5N1 viruses exhibit variable pathogenicity depending on the H5N1 strain and host. HPAI viruses are pathogenic in poultry principally because of a polybasic amino acid insertional mutation in the HA cleavage site, conferring an ability to replicate systemically.…”

Section: How the H5n1 Virus May Be Evolvingmentioning

confidence: 99%

The Next Influenza Pandemic

Taubenberger

Morens²,

Fauci³

2007

JAMA

108

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Section: How the H5n1 Virus May Be Evolvingmentioning

confidence: 99%

The Next Influenza Pandemic

Taubenberger

Morens²,

Fauci³

2007

JAMA

108

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“…For example, type I interferons have strong antiviral activities and can directly inhibit influenza virus replication 1, 2. Meanwhile, excessive cytokine/chemokine responses have been associated with more severe disease during the 2009 H1N1 pandemic,3 lung damage in macaques infected with the 1918 influenza virus,4 and fatal H5N1 infection in humans 5…”

Section: Introductionmentioning

confidence: 99%

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

Talaat

Halsey

Cox

et al. 2018

Influenza Resp Viruses

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BackgroundThe timing of host cytokine responses to influenza vaccination is poorly understood.ObjectivesWe examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV‐related side effects.Patients/MethodsTwenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14.ResultsSerum cytokine responses to TIV were evident as early as 3 hours post‐immunization. Compared to baseline, IFN‐γ and IP‐10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post‐vaccination. Although IL‐8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL‐8 was significantly lower compared to baseline. Interestingly, IL‐8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL‐6, IL‐2, IL‐8, IP‐10, MCP‐1, TNF‐α, TARC, and MCP‐4.ConclusionsSerum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine‐induced reductions in IL‐8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.

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“…The symptoms of influenza are exaggerated by the patient's immune system responding to the virus, rather than by the virus itself. The immune system's prolonged and unbalanced response generates a cytokine storm and causes the lungs to become inflamed and significantly damaged (1)(2)(3)(4)(5)(6)(7)(8). The fight continues in the damaged lung even after the virus is cleared from the body.…”

mentioning

confidence: 99%

Altered T-bet Dominance in IFN-γ–Decoupled CD4+ T Cells with Attenuated Cytokine Storm and Preserved Memory in Influenza

Dutta

Miaw

et al. 2013

The Journal of Immunology

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Cytokine storm has been postulated as one of the major causes of mortality in patients with severe respiratory viral infections such as influenza. With the help of an influenza Ag- specific mouse experimental system, we report that CD4+ T cells contribute effector cytokines leading to lung inflammation in acute influenza. Although virus can no longer be detected from tissues 14 d postinfection, virus-derived Ag continues to drive a CD4+ T cell response after viral clearance. Ag-specific CD4+ T cells proliferate and evolve into memory CD4+ T cells efficiently, but the production of effector cytokines is seriously hampered during this phase. This decoupling of proliferation and effector cytokine production doesn’t appear in conjunction with increased suppression by regulatory T cells or decreased induction of transcription factors. Rather, GATA-3 and ROR-γt levels are elevated when compared with cells that have effector cytokine production. T-bet dominance over GATA-3 and ROR-γt decreases with the disarmament of effector cytokine production. Importantly, upon reinfection, these decoupled cells produce elevated levels of IFN-γ and were effective in virus eradication. These results provide a mechanism through altered T-bet dominance to dampen the cytokine storm without impeding the generation of memory T cells in influenza virus infection.

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Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus

Cited by 870 publications

References 28 publications

The Next Influenza Pandemic

The Next Influenza Pandemic

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

Altered T-bet Dominance in IFN-γ–Decoupled CD4+ T Cells with Attenuated Cytokine Storm and Preserved Memory in Influenza

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