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1.
mBio ; 9(1)2018 01 16.
Article de Anglais | MEDLINE | ID: mdl-29339427

RÉSUMÉ

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect.


Sujet(s)
Prédisposition aux maladies , Sous-type H1N1 du virus de la grippe A/immunologie , Sous-type H2N2 du virus de la grippe A/immunologie , Grippe humaine/immunologie , Grippe humaine/mortalité , Humains , Grippe humaine/virologie , Mexique/épidémiologie , Facteurs de risque , États-Unis/épidémiologie
2.
Biomed Res Int ; 2015: 813047, 2015.
Article de Anglais | MEDLINE | ID: mdl-26346523

RÉSUMÉ

The unpredictable, evolutionary nature of the influenza A virus (IAV) is the primary problem when generating a vaccine and when designing diagnostic strategies; thus, it is necessary to determine the constant regions in viral proteins. In this study, we completed an in silico analysis of the reported epitopes of the 4 IAV proteins that are antigenically most significant (HA, NA, NP, and M2) in the 3 strains with the greatest world circulation in the last century (H1N1, H2N2, and H3N2) and in one of the main aviary subtypes responsible for zoonosis (H5N1). For this purpose, the HMMER program was used to align 3,016 epitopes reported in the Immune Epitope Database and Analysis Resource (IEDB) and distributed in 34,294 stored sequences in the Pfam database. Eighteen epitopes were identified: 8 in HA, 5 in NA, 3 in NP, and 2 in M2. These epitopes have remained constant since they were first identified (~91 years) and are present in strains that have circulated on 5 continents. These sites could be targets for vaccination design strategies based on epitopes and/or as markers in the implementation of diagnostic techniques.


Sujet(s)
Épitopes , Sous-type H1N1 du virus de la grippe A , Sous-type H2N2 du virus de la grippe A , Sous-type H3N2 du virus de la grippe A , Sous-type H5N1 du virus de la grippe A , Vaccins antigrippaux , Simulation numérique , Épitopes/génétique , Épitopes/immunologie , Humains , Sous-type H1N1 du virus de la grippe A/génétique , Sous-type H1N1 du virus de la grippe A/immunologie , Sous-type H2N2 du virus de la grippe A/génétique , Sous-type H2N2 du virus de la grippe A/immunologie , Sous-type H3N2 du virus de la grippe A/génétique , Sous-type H3N2 du virus de la grippe A/immunologie , Sous-type H5N1 du virus de la grippe A/génétique , Sous-type H5N1 du virus de la grippe A/immunologie , Vaccins antigrippaux/génétique , Vaccins antigrippaux/immunologie
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