Mytilus galloprovincialis Myticin C: A Chemotactic Molecule with Antiviral Activity and Immunoregulatory Properties

Abstract

Previous research has shown that an antimicrobial peptide (AMP) of the myticin class C (Myt C) is the most abundantly expressed gene in cDNA and suppressive subtractive hybridization (SSH) libraries after immune stimulation of mussel Mytilus galloprovincialis. However, to date, the expression pattern, the antimicrobial activities and the immunomodulatory properties of the Myt C peptide have not been determined. In contrast, it is known that Myt C mRNA presents an unusual and high level of polymorphism of unidentified biological significance. Therefore, to provide a better understanding of the features of this interesting molecule, we have investigated its function using four different cloned and expressed variants of Myt C cDNA and polyclonal anti-Myt C sera. The in vivo results suggest that this AMP, mainly present in hemocytes, could be acting as an immune system modulator molecule because its overexpression was able to alter the expression of mussel immune-related genes (as the antimicrobial peptides Myticin B and Mytilin B, the C1q domain-containing protein MgC1q, and lysozyme). Moreover, the in vitro results indicate that Myt C peptides have antimicrobial and chemotactic properties. Their recombinant expression in a fish cell line conferred protection against two different fish viruses (enveloped and non-enveloped). Cell extracts from Myt C expressing fish cells were also able to attract hemocytes. All together, these results suggest that Myt C should be considered not only as an AMP but also as the first chemokine/cytokine-like molecule identified in bivalves and one of the few examples in all of the invertebrates.

Antiviral Activity of Myticin C Peptide from Mussel: an Ancient Defense against Herpesviruses

“…Mussel myticins A and B were first described by Mitta et al (41,42) as molecules with antibacterial activity against Grampositive bacteria and with activity against the fungus Fusarium oxysporum and the Gram-negative bacterium Escherichia coli. Myticin C was next identified as an extremely variable antimicrobial peptide with antiviral and antibacterial activities and was also the first chemokine/cytokine-like molecule identified in bivalves and one of the few examples among all invertebrates (26,27).…”

“…Control cells were incubated with FSW. The immunohistochemistry assay of mussel hemocytes was performed using routine procedures: hemocytes were attached to a glass coverslip and incubated overnight (4°C) with anti-myticin C primary antibody (26). Alexa Fluor 488-conjugated anti-rabbit secondary antibody (Life Technologies) was used at a dilution of 1:1,000.…”

An updated molecular basis for mussel immunity

“…Myticin C has been shown to act not only as an AMP, but also as an immuno-modulating molecule, due to its chemotactic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 properties [159]. Based on transcriptomic evidence, we can confirm that no additional myticin-like sequences are expressed in mussel.…”

“…In essence, most bivalve cytokines remains elusive due to a lack of similarity with vertebrates and a similar role could be shared by completely different molecules such as myticin C: for long time considered to strictly act as an AMP, experimental data suggested its cytokine function, since extracts of cells expressing myticin C were able to attract hemocytes [159]. In brief, the available evidence for bivalve cytokines is fragmentary and their dentification is still mostly limited to a few evolutionarily conserved molecules.…”

Biotecnología marina y acuicultura

“…En animales tan próximos a nosotros como son los mejillones, se ha descubierto una nueva clase de péptidos antimicrobianos, con actividades antivirales y antibacterianas, llamada myticina C (Balseiro et al, 2011). Los péptidos antimicrobianos (AMP) son pequeñas moléculas, presentes en la gran mayoría de organismos, que actúan como antibióticos naturales ante determinadas enfermedades.…”