Ifitm3 restricts the morbidity and mortality associated with influenza pdf

Aug 27, 20 the ifitm3 variant explored by everitt et al. To test the role of ifitm3 in human influenza virus infection. Interferoninduced transmembrane protein 3 ifitm3 is a component of isg interferonstimulated gene family. In the lancet, danielle iuliano and colleagues1 have attempted to estimate the global mortality burden of seasonal influenza. If you click continue well assume that you are happy to receive all cookies and you wont see this message again. Ifitm3 restricts the morbidity and mortality associated with influenza nasa ads the 2009 h1n1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Histone demethylase lsd1 restricts influenza a virus. Request pdf ifitm3 restricts the morbidity and mortality associated with influenza the 2009 h1n1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the. Ifitm3 and susceptibility to respiratory viral infections.

However, some different conclusions were found in our study. Influenzaassociated morbidity and mortality in young and. Ifitm3 restricts the morbidity and mortality associated with influenzaeveritt ar, clare s, pertel t, et al. Lack of truncated ifitm3 transcripts in cells homozygous. Mar 25, 2012 ifitm3 restricts the morbidity and mortality associated with influenza.

Diseases associated with ifitm3 include influenza, severe and influenza. What have we learned about influenza deaths in children. Ifitm3 restricts the morbidity and mortality associated with influenza everitt et al. This study provides a much needed update to the often cited but unsubstantiated whoattributed estimate of 250 000500 000 annual influenza deaths. Influenzaassociated pediatric mortality 2004 case definition. Ifitm3 is a ubiquitously expressed antiviral protein that inhibits multiple human pathogenic viruses, including influenza a virus iav. Ccr5 deficiency predisposes to fatal outcome in influenza. While it is clear that ifitm3 restricts viral infection by preventing release of viral particles into the cytoplasm, the mechanism by which it achieves this is still unclear. Influenza a virus replicates to higher levels in ifitm3. Panel policy and public health implications of repeated. Excess mortality has been documented since 1889, and the infamous 1918 outbreak confirmed that influenza was truly one of the last major plagues. Clifford c a communicable disease surveillance centre, public health laboratory service, london nw9 5eq, united kingdon b national institute for biological standards and control, holly hill, hampstead, london nw3 6rb, united kingdon c department of community. Rosalind louise smyth cbe mbbs md frcpch fmedsci born 28 september 1958. Genes in humans associated with more severe influenza 2.

In 53 individuals with severe influenza infection who required hospitalization as a result of pandemic h1n109 or seasonal influenza virus infection in 20092010, everitt et al. Pdf ifitm3 restricts the morbidity and mortality associated. Ifitm3 restricts the morbidity and mortality associated with. Astroglial ifitm3 mediates neuronal impairments following. Mice lacking ifitm3 display fulminant viral pneumonia when challenged with a normally lowpathogenicity influenza virus, mirroring the destruction inflicted by the highly pathogenic 1918 spanish influenza. Among its related pathways are innate immune system and interferon gamma signaling. The interferon ifn induced transmembrane protein ifitm3 is an important antiviral factor shown to restrict replication of around seventeen, mostly enveloped rna viruses including influenza a virus iav, human immunodeficiency virus 1.

Presence of the c allele results in a synonymous change but alters the first splice acceptor site and may be associated with an ifitm3. To test the role of ifitm3 in human influenza virus. Influenza, influenzaassociated mortality, and novel. Severe morbidity and mortality associated with influenza in. By aaron r everitt, simon clare, thomas pertel, sinu p john, rachael s wash, sarah e smith, christopher r chin, eric m feeley, jennifer s sims, david j adams, helen m wise, leanne kane, david goulding, paul digard, verneri anttila, j kenneth baillie, tim s walsh, david a hume, aarno palotie, yali xue, vincenza colonna, chris tylersmith, jake dunning, stephen b gordon, rosalind l smyth, peter. Ann arbor, michigan because of their dramatic impact, morbidity and mortality associ ated with influenza have been recognized since at least the time of elizabeth i of england. The mosaic investigators, smyth rl, openshaw p, dougan g, brass al, kellam p.

Ifitm3 protects the heart during influenza virus infection. Absence of ifitm3 expression was verified in the ifitm3. It plays a critical role in the immune systems defense against swine flu, where heightened levels of ifitm3 keep viral levels low, and the removal of ifitm3 allows the virus to multiply unchecked. Department of health, education and welfare, public health service, 1957. Challenges in reducing influenzaassociated mortality the. Ifitm3 was identified in a functional genomic screen as mediating resistance to influenza a. In the article published in nature on 25th march 2012, everitt and colleagues describe an association between a gene which codes for an interferon inducible transmembrane protein, ifitm3, and susceptibility to influenza infection 1.

This association has been verified by this metaanalysis with half the data coming from 2016 and 2017 articles. Influenza update 30 march 2012 1 influenza update n 156 30 march 2012 summary this influenza season started late but seems to be reaching the peak or is decreasing in most countries of the northern hemisphere temperate regions. We use cookies to ensure that we give you the best experience on our website. Ifitm3 restricts the morbidity and mortality associated with influenza. Provisional cases of infrequently reported notifiable diseases influenza is an acute respiratory illness, caused by influenza a, b, and c viruses, that occurs in local outbreaks or seasonal epidemics. Ifninduced transmembrane protein 3 ifitm3 are associated with susceptibility to severe influenza, but whether ifitm3 deficiencies contribute to cardiac dysfunction during infection is unclear. Interferoninduced transmembrane 3 ifitm3 is known to restrict the entry of a range of enveloped viruses.

This suggests underlying genetic determinants that govern infection severity. Since ifitm3 polymorphisms are among the only human genetic factors that have been reproducibly associated with hospitalization and mortality during influenza virus infection, our findings are relevant to. A surveillance case definition is a set of uniform criteria used to define a disease for public health surveillance. The role of murine and human ifitm3 in fighting influenza infection was. Even now, fear of a viral pandemic is widespread, fueling recent disaster movies such as contagion and the ongoing controversy over publication of experiments on enhancing influenza virulence. The lancet excess morbidity and mortality associated with influenza in england and wales hilarye. As mentioned above, genetic variation within ifitm3 has been associated with influenza infection severity. Sep 10, 2019 we discovered that ifitm3 prevents efficient dissemination and replication of influenza virus in heart tissue, thereby limiting cardiac fibrosis and electrical dysfunction during infection.

Since ifitm3 polymorphisms are among the only human genetic factors that have been reproducibly associated with hospitalization and mortality during influenza virus infection, our findings are relevant. Influenza pandemics can lead to substantially increased morbidity and mortality rates compared with seasonal influenza. We discovered that ifitm3 prevents efficient dissemination and replication of influenza virus in heart tissue, thereby limiting cardiac fibrosis and electrical dysfunction during infection. Influenza a virus replication is persistent and associated with increased cell death and exaggerated proinflammatory responses in the lungs of mice lacking ifitm3. Observations on excess mortality associated with epidemic. Severe acute respiratory infections was mainly observed in the age group above 65 years. Ifitm3 restricts the morbidity and mortality associated with influenza the harvard community has made this article openly available. The panel summarises the risk factors associated with severe illness, complications, or mortality due to influenza. Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Similarly, the enrichment of the rs12252 callele in those hospitalized with influenza infections, together with the decreased ifitm3 levels and the increased infection of the ccallele cells in vitro, suggests that ifitm3 also plays a pivotal role in defence against human influenza virus infections. While the relationship between this genetic variation and the progress of hcc remains unclear.

The association between ifitm3 and hepatocellular carcinoma hcc has been reported. Ifitm3 restricts human metapneumovirus infection the. Association between rs12252 and influenza susceptibility and severity. Thus, ifitm3 restricts the morbidity and mortality associated with influenza everitt et al. It has been suggested that rs12252c results in expression of a truncated ifitm3 protein lacking the first 21 amino acids. The single nucleotide polymorphism rs12252c within ifitm3 has been shown to be associated with severe influenza a virus infection. Antigenic shift is a sporadic event, restricted to influenza a viruses, and refers to the introduction into. A new genetic virological factor in influenza viruses that modulates the host response. Therefore, enhanced pathogenesis to diverse influenza viruses is attributable to loss of ifitm3 expression and consequential changes in immune defence of the lungs. Both the magnitude and breadth of the ifitm proteins in vitro effects suggest that they are critical for intrinsic resistance to such viruses, including influenza viruses. Amphotericin b increases influenza a virus infection by. Ifitm3 knockout ko mice and humans with deleterious ifitm3 gene polymorphisms experience severe influenza virus infections, confirming the importance of this protein in antiviral defense in vivo.

Together these data reveal that the action of a single intrinsic immune effector, ifitm3, profoundly alters the course of influenza virus infection in mouse and man. Although most public health programs target persons thought to be at higher risk of complications of influenza for vaccination. Morbidity and mortality weekly report mmwr may 24, 20 vol. Evaluation of ifitm3 rs12252 association with severe. Association between rs12252 and influenza susceptibility. Snps within ifitm3, rs12252 and rs34481144, have been demonstrated to alter severity of influenza infection 41, 42, 56.

Interferoninduced transmembrane protein 3 ifitm3 is a protein that in humans is encoded by the ifitm3 gene. Effects of ifitm3 on hmpv have not yet been adequately investigated. Mmwr morbidity and mortality weekly report mmwr august 27, 2010 vol. Ifitm3 restricts the morbidity and mortality associated. Presence of the c allele results in a synonymous change but alters the first splice acceptor site and may be associated with an ifitm3 splice variant that. The 2009 h1n1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. Influenza associated pediatric mortality 2004 case definition recommend on facebook tweet share compartir note. Epidemiology and infection association between rs12252 and. This observation has been further advanced by a recent study that shows that a single. Since this initial report, the centers for disease control and prevention have continued to periodically report their findings from the passive influenzaassociated pediatric mortality surveillance system. We show that ifitm3 deficiency in a new k nockout ko mouse model increases weight loss and mortality following influenza virus infections.

What have we learned about influenza deaths in children and. Ifitm3 restricts the morbidity and mortality associated with influenza abstract the 2009 h1n1 influenza pandemic showed the speed with which a novel respiratory virus can spread and the ability of a generally mild infection to induce severe morbidity and mortality in a subset of the population. The genomes project currently lists 15 nonsynonymous, 15 synonymous, 1 stopsite gaining, and 1 possible splicesite altering singlenucleotide polymorphism snp in the ifitm3. Because of their dramatic impact, morbidity and mortality associated with influenza have been recognized since et lent the time of elizabeth i of england. Interferoninduced transmembrane protein 3 ifitm3 plays a critical role in the immune systems defence against influenza. Ifitm3 interferon induced transmembrane protein 3 is a protein coding gene. Whereas comorbidities are present in 50 % of fatal cases, 2550 % of deaths are in apparently healthy individuals. Influenza a viruses can also cause sporadic infections or spread worldwide. Since this initial report, the centers for disease control and prevention have continued to periodically report their findings from the passive influenza associated pediatric mortality surveillance system. Interferoninduced transmembrane protein3 rs12252cc is. Clinical illness follows a short incubation period and presentation ranges from asymptomatic to fulminant, depending on the characteristics of both the virus and the individual host. The famed spanish flu pandemic of 1918 killed more people than did world war iand more people in a single year than did 4 years of the bubonic plague in medieval europe. The genisis, the mosaic investigators, smyth rl, openshaw p, dougan g, brass al, kellam p. Interferoninducible transmembrane ifitm protein 3 is shown to be an innate defence mechanism against viral infection in vivo.

While immunization programs remain the cornerstone for the control of influenza, each year influenza is associated with considerable respiratory and allcause mortality. Further to ifitm3 s role in restriction of hp h5n1 avian influenza 7, we also show that it limits infection by recent human influenza a isolates and influenza b virus supp. The authors used countryspecific, influenzaassociated excess respiratory mortality estimates from 1999 to 2015, to. Percent of adults aged 65 and over who received an influenza vaccination during the past 12 months. Brass and colleagues now show that a widely used antifungal therapy, ambisome, prevents ifitm3 from blocking iav replication and that mice given ambisome succumb to a normally mild influenza virus infection. A genetic finding could help explain why influenza becomes a lifethreatening disease to some people while it has only mild effects in others.

Ifitm3 protects the heart during influenza virus infection pnas. Change in body mass a and survival b of wt and ifitm3. Early release of selected estimates based on data from the 2018 national health interview survey, data table for figure 4. Severe morbidity and mortality associated with influenza in children and young adults michigan, 2003 during late january 2003, the michigan department of community health mdch received reports of severe unexplained illnesses and deaths in children and young adults aged influenza a infection from an animal source is the inability of available tests to subtype the detected virus.