H1N1 versus H5N1 hemagglutinins: A possible differential immunologic impact on neurodevelopment

Background and objectiveTo understand the role of influenza infections during pregnancy in the genesis of mental disorders in the adult offspring, we explored the potential peptide crossreactivity between influenza hemagglutinin (HA) and human neurodevelopmental antigens.MethodsInfluenza A H1N1 and H5N1 HAs and a random set of neurodevelopmental proteins were searched for common epitopic signatures that might underlie injury patterns during fetal brain development using Immune Epitope Database resource.ResultsWe find an extensive epitopic peptide matching that is consistent with a potential for influenza A H1N1 infection to preferentially affect axon extension and fasciculation, and for influenza A H5N1 infection to hit synaptogenesis. Indeed, H1N1 HA hosts epitopic sequences that might cross-react with axon fasciculation antigens, by sharing H1N1 HA – but not H5N1 HA – epitopic peptide segments with human fasciculation and elongation protein zeta-2 (FEZ2), neurofascin (NFASC), roundabout homolog 1 (ROBO1), and neural cell adhesion molecule L1 (L1CAM). Instead, H5N1 HA shares epitopic peptide segments with human synaptogenesis-associated antigens such as voltage-dependent calcium channel subunit alpha-1H (CAC1H) and alpha-1D (CAC1D). Interestingly, pentapeptides shared between HAs and neurodevelopment-associated proteins are also present in other infectious agents such as herpesviruses and Toxoplasma gondii. The pentapeptide overlap is of particular intensity in the protozoan parasite.ConclusionsThese findings may help explain the discording epidemiological data on the relationship between prenatal influenza infection and the increased risk of neurodevelopmental pathologies in the offspring.