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.

The Guillain–Barrè peptide signatures: from Zika virus to Campylobacter, and beyond

“…In fact, the magnitude of such a peptide sharing leads to predict a high extent of cross-reactive immune responses following infections in the human host. [66][67][68][69][70][71][72] Here, we focus on the issue of multiple cross-reactivity and analyze the molecular connections between infectious pathogens related to GBS. We report on the presence of minimal immune determinants in the human host and repeatedly shared among infectious agents so different as the flaviviruses ZIKV, DENV, WNV, and YFV and the bacteria M. pneumoniae and C. jejuni.…”

Respiratory virus-induced heterologous immunity

“…Pre-existing HA 391-410 -speci c CD4 + T m cells showed expansion a er seasonal IV vaccination. ese T m cells expanded a er stimulation with the Trichomonas vaginalis (T. vaginalis)-derived hypothetical protein [118][119][120][121][122][123][124][125][126][127][128][129][130] -and the Finegoldia magna (F. magna)derived hypothetical protein [131][132][133][134][135][136][137][138][139][140][141][142][143] peptide in vitro (Tab. 1).…”

“…Narcolepsy was associated with the IV A(H1N1) pdm09 vaccine Pandemrix® (GlaxoSmithKline, London, UK) [109] and also with A(H1N1)pdm09 infection [110]. Recently, Ahmed et al [111], showed that the Pandemrix® vaccine, in some HLA-DQB1*06:02-positive individuals, induced IV A NP [111][112][113][114][115][116][117][118][119][120][121] antibodies, which were cross-reactive to the hypocretin receptor 2 [34][35][36][37][38][39][40][41][42][43][44][45] (Tab. 2).…”

“…Maternal infection, including in uenza, has been suggested to play a role in the development of psychiatric disorders in the child [118]. Lucchese et al identi ed in uenza epitope mimics in multiple neuronal proteins ( [119,120]; Tab. 2).…”

Development of a novel clustering tool for linear peptide sequences

“…The tool is powerful for visualization purposes, but is not well suited to resolve redundancy of sequences in separate and specific clusters, and is also not ideal to analyse sequences that may cluster together, but that are in fact derived from unrelated antigens. Indeed, the identification of regions of homology between unrelated sequences has been associated with a number of important biological phenomena, like molecular mimicry, allergen cross‐reactivity, and microbiome modulation of adaptive immune responses . Clustering epitope reactivity may also be of interest to generate epitope ‘megapools’ of minimal composition by elimination of potentially redundant sequences based on a specific degree of protein similarities …”