title: Peptide sharing between influenza A H1N1 hemagglutinin and human axon guidance proteins.
abstract: Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus.
authors: To whom correspondence should be addressed; tel: +39.080.544.3321, fax: +39.080.544.3317, e-mail: dkanduc@gmail.com.
authors: Guglielmo
authors: G
authors: Lucchese
authors: Giovanni
authors: G
authors: Capone
authors: Darja
authors: D
authors: Kanduc
mesh_terms: D001321:Autistic Disorder / Q000209:etiology; D001369:Axons / Q000737:chemistry*; D001714:Bipolar Disorder / Q000209:etiology; D000939:Epitopes / Q000737:chemistry; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D012559:Schizophrenia / Q000209:etiology
chemical_list: D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009419:Nerve Tissue Proteins; D019151:Peptide Library; D010455:Peptides
keywords: autism; bipolar disorder; hemagglutinin; immune cross-reactivity; influenza A H1N1 virus; schizophrenia
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