tetano
Editor, Senior Moderator
Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins
Guglielmo Lucchese1,2,
Giovanni Capone3 and
Darja Kanduc*,3
+ Author Affiliations
1 Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy;
2 Brain and Language Laboratory, Cluster of Excellence ?Languages of Emotions,? Department of Philosophy and Humanities, Free University of Berlin, Berlin, Germany;
3 Department of Biosciences, Biotechnologies and Pharmacological Sciences, University of Bari, Bari, Italy
↵ *To whom correspondence should be addressed; tel: +39.080.544.3321, fax: +39.080.544.3317, e-mail: dkanduc@gmail.com
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.
http://schizophreniabulletin.oxfordjournals.org/content/early/2013/01/31/schbul.sbs197.short
Guglielmo Lucchese1,2,
Giovanni Capone3 and
Darja Kanduc*,3
+ Author Affiliations
1 Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy;
2 Brain and Language Laboratory, Cluster of Excellence ?Languages of Emotions,? Department of Philosophy and Humanities, Free University of Berlin, Berlin, Germany;
3 Department of Biosciences, Biotechnologies and Pharmacological Sciences, University of Bari, Bari, Italy
↵ *To whom correspondence should be addressed; tel: +39.080.544.3321, fax: +39.080.544.3317, e-mail: dkanduc@gmail.com
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.
http://schizophreniabulletin.oxfordjournals.org/content/early/2013/01/31/schbul.sbs197.short