Giovanni Capone

Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins

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.

Reviewing the role of peptide rarity in bacterial toxin immunomics.

In the past decade, renewed efforts have been made toward the development of vaccines against cancers, infectious agents, autoimmune diseases, and allergies. These efforts have led to the accumulation of numerous peptide sequences experimentally validated as epitopes. However, the factors that render a peptide immunogenic and, more generally, the nature of the antigen-antibody recognition process remain unclear. Based on the hypothesis that potential epitopes correspond to rare sequences and/or structures, we analytically review the data on the molecular structure and properties of immunoreactive sequences derived from (or evoked by) Clostridium tetani, Bacillus anthracis, and C. botulinum toxins. A cohesive picture emerges when peptide motifs are absent or scarcely represented in endogenous self proteins as they define a common immune signature of bacterial toxin B-cell immune determinants. Likewise, the scientific literature also shows that the heavy chain third complementarity-determining regions (CDR3s) from antitoxin antibodies are characterized as being formed by rare peptide sequences. The present meta-analysis aims to provide a key to understanding the molecular nature of the immune recognition process and, in turn, to contribute to the development of effective and safe peptide-based diagnostic tools and vaccine applications.

Codon number shapes peptide redundancy in the universal proteome composition.

The proteomes catalogued in the UniRef100 database were collected into a single proteome set and examined for actual versus theoretical pentapeptide occurrences. We found a highly diversified degree of pentapeptide redundancy. Numerically, 953 pentamers are expressed only once in the protein world, whereas 103 pentamers occur more than 50,000 times. Moreover, it seems that 417 potentially possible pentapeptides are not present in the protein world. On the whole, tracing the redundancy profile of the protein world as a function of pentapeptide occurrences reveals a quasi-Gaussian curve, with tails representing scarcely and repeatedly occurring 5-mers. Analysis of physico-chemical-biological parameters shows that codon number is the main factor influencing and favoring specific pentapeptide frequencies in the universal proteome composition. That is, when compared to the set of never-expressed 5-mers, the pentapeptides frequently represented in the universal proteome are endowed with a higher number of multi-codonic amino acids. In contrast, the bulkiness degree and the hydrophobicity level play a smaller role. Unexpectedly, the heat of formation of pentapeptide appears to have the least influence.

West Nile virus diagnosis and vaccination: using unique viral peptide sequences to evoke specific immune responses

West Nile virus (WNV) infection may be associated with fever, neurologic disorders, and acute flaccid paralysis as a final clinical outcome. In spite of the numerous WNV infection outbreaks in Africa, Eurasia, Australia, and North America and notwithstanding an intense research effort for developing effective anti-WNV vaccines, currently no immunopreventive or therapeutic approaches are available. Moreover, antigenic cross-reactivity among flaviviruses can make difficult WNV serodiagnosis. Here we analyze the primary sequence of WNV polyprotein searching for peptide modules that might be utilized to design targeted diagnostic tools and anti-WNV vaccines for use in humans. To this aim, we applied the low-similarity hypothesis, according to which rare peptide sequences are more likely immunogenic than frequent peptide sequences. We report on a set of peptide sequences unique to the WNV, the immunogenic potential of which appears to be confirmed by immunological data cataloged at the Immune Epitope Data Base resource.

The oligodeoxynucleotide sequences corresponding to never-expressed peptide motifs are mainly located in the non-coding strand

BackgroundWe study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides.ResultsWe find that only DNA context-dependent constraints (such as oligodeoxynucleotide sequence location in the minus strand, introns, pseudogenes, frameshifts, etc.) provide a coherent mechanistic platform to explain the occurrence of never-expressed versus frequent pentapeptides in the protein world.ConclusionsThis study is of importance in cell biology. Indeed, the rarity (or lack of expression) of specific 5-mer peptide modules implies the rarity (or lack of expression) of the corresponding n-mer peptide sequences (with n > 5), so possibly modulating protein compositional trends. Moreover the data might further our understanding of the role exerted by rare pentapeptide modules as critical biological effectors in protein-protein interactions.

A quantitative description of the peptide sharing between poliovirus and Homo sapiens

In the present study, we analyze the peptide commonality between poliovirus polyprotein and the human proteins. We report on the following findings: (1) the extent of polio peptide overlap on the human proteome is high, and involves the entire viral polyprotein; (2) viral peptide matching affects human proteins linked to fundamental cellular functions. The data may help to further our understanding of the relationships between poliovirus and the human host.

Peptide matching between Epstein–Barr virus and human proteins

Epstein-Barr virus proteins were examined for amino acid sequence matching to human proteins at the decapeptide level. We report that numerous EBV peptides of different length (from 10- to 13-mer) are present in 28 human proteins. The viral vs. human peptide overlap mainly involves the glycine-rich region allocated in the NH2 terminus of Epstein-Barr nuclear antigen 1 protein and host cellular components that play crucial roles in basic biochemical pathways, such as chromatin remodeling, RNA splicing, transmission across chemical/electrical synapses, and neurogenesis, and that, when altered, may characterize various pathologies such as immunodeficiency, systemic lupus erythematosus, myelination, and speech disorders. The present results might contribute to understand and define the (physio) pathological relationships and interactions occurring between EBV and the human host.

Peptides in Oral Diseases

The oral cavity is home to numerous viruses and micro-organisms recognized as having a role in various oral diseases as well as in infections in other parts of the body. Indeed, in general a microbial infection underlies or is believed to underlie the ample spectrum of oral diseases, from tooth enamel decay to periodontal lesions, from candidiasis to virus-induced oral squamous cell carcinomas, and bullous autoimmune oral disorders. This clinico-pathological context stresses the need of targeted therapies to specifically kill infectious agents in a complex environment such as the oral cavity, and explains the current interest in exploring peptide-based therapeutic approaches in oral and dental research. Here, we review the therapeutic potential of antimicrobial peptides such as LL-37, beta defensins, adrenomedullin, histatins, and of various peptides modulating gene expression and immuno-biological interaction(s) in oral diseases.

Evidence for a vast peptide overlap between West Nile virus and human proteomes.

The primary amino acid sequence of West Nile virus (WNV) polyprotein, GenBank accession number M12294, was analyzed by computional biology. WNV is a mosquito‐borne neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. Using pentapeptides as scanning units and the perfect peptide match program from PIR International Protein Sequence Database, we compared the WNV polyprotein and the human proteome. WNV polyprotein showed significant sequence similarities to a number of human proteins. Several of these proteins are involved in embryogenesis, neurite outgrowth, cortical neuron branching, formation of mature synapses, semaphorin interactions, and voltage dependent L‐type calcium channel subunits. The biocomputional study suggest that common amino acid segments might represent a potential platform for further studies on the neurological pathophysiology of WNV infections.

Fractal analysis of mucosal microvascular patterns in oral lichen planus: a preliminary study

OBJECTIVES The objective of this study was to assess local vascular architecture in atrophic-erosive oral lichen planus (OLP). MATERIALS AND METHODS We investigated the capillary structure of the oral mucosa in 31 patients with OLP and 32 healthy controls. Capillaries images were captured in vivo through a capillaroscope. We applied fractal analysis to quantify the microvasculature morphometric changes in the oral mucosa of atrophic-erosive OLP patients in terms of their fractal dimension (D). RESULTS The oral vascular networks of atrophic-erosive OLP lesions had a significantly higher D, both in buccal mucosae (D=1.167, P=.019) and in tongue (D=1.196, P=.038), compared with the control population (1.123 for both locations, respectively). CONCLUSIONS The present study confirms previous literature data on a close relationship between abnormal vascular architecture and atrophic-erosive OLP. Fractal analysis provided a quantitative descriptor of the complexity of the vascular patterns, which increases in the OLP samples. These data may provide new information on the OLP pathogenesis, as well as serve as morphologic quantifiers for monitoring treatment strategies.