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

Abstract

Little is known about the antiviral response in mollusks. As in other invertebrates, the interferon signaling pathways have not been identified, and in fact, there is a debate about whether invertebrates possess antiviral immunity similar to that of vertebrates. In marine bivalves, due to their filtering activity, interaction with putative pathogens, including viruses, is very high, suggesting that they should have mechanisms to address these infections. In this study, we confirmed that constitutively expressed molecules in naive mussels confer resistance in oysters to ostreid herpesvirus 1 (OsHV-1) when oyster hemocytes are incubated with mussel hemolymph. Using a proteomic approach, myticin C peptides were identified in both mussel hemolymph and hemocytes. Myticins, antimicrobial peptides that have been previously characterized, were constitutively expressed in a fraction of mussel hemocytes and showed antiviral activity against OsHV-1, suggesting that these molecules could be responsible for the antiviral activity of mussel hemolymph. For the first time, a molecule from a bivalve has shown antiviral activity against a virus affecting mollusks. Moreover, myticin C peptides showed antiviral activity against human herpes simplex viruses 1 (HSV-1) and 2 (HSV-2). In summary, our work sheds light on the invertebrate antiviral immune response with the identification of a molecule with potential biotechnological applications. IMPORTANCESeveral bioactive molecules that have potential pharmaceutical or industrial applications have been identified and isolated from marine invertebrates. Myticin C, an antimicrobial peptide from the Mediterranean mussel (Mytilus galloprovincialis) that was identified by proteomic techniques in both mussel hemolymph and hemocytes, showed potential as an antiviral agent against ostreid herpesvirus 1 (OsHV-1), which represents a major threat to the oyster-farming sector. Both hemolymph from mussels and a myticin C peptide inhibited OsHV-1 replication in oyster hemocytes. Additionally, a modified peptide derived from myticin C or the nanoencapsulated normal peptide also showed antiviral activity against the human herpesviruses HSV-1 and HSV-2. Therefore, myticin C is an example of the biotechnological and therapeutic potential of mollusks.

Bivalve transcriptomics reveal pathogen sequences and a powerful immune response of the Mediterranean mussel (Mytilus galloprovincialis)

“…Still, knowledge about the antiviral response in bivalves, as in all invertebrates, is scarce. The discussion about whether invertebrates possess antiviral immunity is ongoing and further enhanced by recent works, such as the study presented by Novoa et al (2016). In this study, they confirmed that constitutively expressed myticins in naïve mussels made oyster hemocytes resistant to ostreid herpesvirus 1 (OsHV-1).…”

Transcriptomic Analysis Reveals the Wound Healing Activity of Mussel Myticin C

“…Myticin C is an antimicrobial peptide widely studied in mussels. Some of its functions are directly related to the killing of pathogens: its antibacterial [8] and antiviral properties [10,21] have been reported. In line with these properties, one of the most expressed genes in the transcriptome analysis is the tripartite motif-containing protein 56 (TRIM56).…”

“…Hemocytes are capable of encapsulating and phagocyting foreign particles or pathogens, as well as synthesizing and releasing cytotoxic factors [8], including AMPs that represent key components of the mussel immune system. These small cationic peptides are cysteine-rich molecules, and are traditionally involved in the response to bacteria, some fungi, and viruses [9,10].…”

“…Myticin C is constitutively expressed in mussel hemocytes and stored in vesicles in the cytoplasm [10]. From a functional point of view, myticin C shows antibacterial activity [8] and antiviral function against fish rhabdovirus [21], ostreid herpesvirus (OsHV-1), and even human herpes simplex (HSV-1 and HSV-2) [10]. Recently, apart from the antimicrobial activity, a new function related to damage-associated molecular pattern (DAMP) response and response to tissue injury has been suggested [22].…”

The blue mussel inside: 3D visualization and description of the vascular-related anatomy of Mytilus edulis to unravel hemolymph extraction

“…In mussels, the hemocytes are also involved in the host immune system as half of the genes expressed by these cells are antimicrobial peptides such as myticins, mytilins and myticilins 17 . Myticin C for example inhibits the replication of bacteria 18 , fish viruses 19 , and human herpesvirus 20 . In adult oysters, the gill was reported to be the potential hematopoietic site 21,22 .…”