Article

Antimicrobial Peptides as Model Molecules for the Development of Novel Antiviral Agents in Aquaculture

IBMC, Miguel Hernández University, 03202, Elche, Spain.
Mini Reviews in Medicinal Chemistry (Impact Factor: 2.9). 09/2009; 9(10):1159-64. DOI: 10.2174/138955709789055171
Source: PubMed

ABSTRACT

Antimicrobial peptides (AMPs) are one of the components of the non-specific immune system that operate first lines of protection in many animal species including fish. They exert broad-spectrum antimicrobial activity, apart from many other potential roles in innate immunity, and represent a promising class of antiviral agents. Recent advances in understanding the mechanisms of their antiviral action(s) indicate that they have a dual role in antiviral defence, acting not only directly on the virion but also on the host cell. Despite the acute problems of viral diseases and restrictions in using chemicals in aquaculture, few but successful attempts to assess the antiviral activities of fish AMPs have been reported. This review focuses on the antiviral activities and mechanisms of action of some AMPs, and their potential relevance in the aquaculture industry, one of the most important sources of fishery products in the near future. It is a matter of notable concern to understand whether the AMPs can be used as model molecules for designing antiviral drugs that might help to solve the problems with viruses in the fish farming industry worldwide. In addition, because fish rely more heavily on their innate immune defences than mammals, they might constitute a potential rich source of antiviral compounds for fighting against mammalian viral infections.

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    • "Because some reports have shown that AMPs possess antiviral activity against enveloped and non-enveloped viruses [20], [21], with some of them acting across species [22], [23], the antiviral activity of recombinant Myt C was studied against the fish enveloped and non-enveloped viruses, VHSV and IPNV, respectively. The results clearly showed that Myt C could be considered as an invertebrate antiviral immune effector, at least against the fish viruses that were tested in this study. "
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    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.
    Full-text · Article · Aug 2011 · PLoS ONE
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    • "In fish, several AMPs such us pleurocidin, daxin, misgurnin, piscidin , moronecidin, parasin, defensins and hepcidin, have been found (Casadei et al., 2009; Falco et al., 2009; Rajanbabu and Chen, 2010). Among defensin types, only ␤-defensin genes have been identified so far but scarcely characterised at functional level. "
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    ABSTRACT: Antimicrobial peptides (AMPs) are important mediators of the innate immune response against bacteria and viruses. We have found a β-defensin (BD) gene searching the expressed sequence tags (ESTs) of the teleost fish gilthead seabream (Sparus aurata). The clone contains an open reading frame of 201 bp mRNA that encodes a putative seabream β-defensin (saBD) propeptide of 66 amino acids containing the six conserved cysteines as the main signature of this AMP. The phylogenetic tree shows that saBD, and its fish orthologues, are closely related to the human BD-4. Transcripts of the saBD gene were mainly detected by real-time PCR in the skin, peritoneal leucocytes and head-kidney but scarcely expressed in the peripheral blood. Interestingly, head-kidney leucocytes incubation with synthetic unmethylated CpG oligodeoxynucleotides and bacterial DNA up-regulated the saBD gene expression. Recombinant protein (saBD-V5-His) was expressed in the HEK293 cell line and its functional activity determined. First, seabream head-kidney leucocytes showed chemotactic activity towards supernatants containing saBD-V5-His whilst failed to do so to human recombinant BD-1 y BD-4. Moreover, both cell lysates and supernatants containing saBD-V5-His showed strong antimicrobial activity against Vibrio anguillarum (a seabream pathogenic bacterium) and Bacillus subtilis whilst little on other fish pathogens such as Vibrio harvey and Photobacterium damselae. Further studies will elucidate the existence of other BD genes and their implications on the seabream defense against bacteria and virus.
    Full-text · Article · Jul 2011 · Molecular Immunology
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    • "Other transcripts only appeared differentially expressed in one of the arrays, such as il17 d and il22 (Table 2). Both il17 and il22 are produced by T helper 17 (Th17) cells [51] to synergistically induce antimicrobial peptides [52] in human keratinocytes [53]. At this respect, 2 antimicrobial peptides increased in VHSV-infected zebrafish fins and organs, including the hepcidin antimicrobial peptide 1 (hamp1) and the β defensin (defbl2) genes, the former one with p > 0.05. "
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    ABSTRACT: Despite rhabdoviral infections being one of the best known fish diseases, the gene expression changes induced at the surface tissues after the natural route of infection (infection-by-immersion) have not been described yet. This work describes the differential infected versus non-infected expression of proteins and immune-related transcripts in fins and organs of zebrafish Danio rerio shortly after infection-by-immersion with viral haemorrhagic septicemia virus (VHSV). Two-dimensional differential gel electrophoresis detected variations on the protein levels of the enzymes of the glycolytic pathway and cytoskeleton components but it detected very few immune-related proteins. Differential expression of immune-related gene transcripts estimated by quantitative polymerase chain reaction arrays and hybridization to oligo microarrays showed that while more transcripts increased in fins than in organs (spleen, head kidney and liver), more transcripts decreased in organs than in fins. Increased differential transcript levels in fins detected by both arrays corresponded to previously described infection-related genes such as complement components (c3b, c8 and c9) or class I histocompatibility antigens (mhc1) and to newly described genes such as secreted immunoglobulin domain (sid4), macrophage stimulating factor (mst1) and a cluster differentiation antigen (cd36). The genes described would contribute to the knowledge of the earliest molecular events occurring in the fish surfaces at the beginning of natural rhabdoviral infections and/or might be new candidates to be tested as adjuvants for fish vaccines.
    Full-text · Article · Sep 2010 · BMC Genomics
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Questions & Answers about this publication

  • Ali Muhammad Mastoi asked a question in Innate Immune Response:
    What are the antimicrobial peptides and what is their role in immune response ?
    I am here in Malaysia Ph.D student in Institute Tropical of aquaculture University Malaysia Terengganau
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      [Show abstract] [Hide abstract]
      ABSTRACT: Antimicrobial peptides (AMPs) are one of the components of the non-specific immune system that operate first lines of protection in many animal species including fish. They exert broad-spectrum antimicrobial activity, apart from many other potential roles in innate immunity, and represent a promising class of antiviral agents. Recent advances in understanding the mechanisms of their antiviral action(s) indicate that they have a dual role in antiviral defence, acting not only directly on the virion but also on the host cell. Despite the acute problems of viral diseases and restrictions in using chemicals in aquaculture, few but successful attempts to assess the antiviral activities of fish AMPs have been reported. This review focuses on the antiviral activities and mechanisms of action of some AMPs, and their potential relevance in the aquaculture industry, one of the most important sources of fishery products in the near future. It is a matter of notable concern to understand whether the AMPs can be used as model molecules for designing antiviral drugs that might help to solve the problems with viruses in the fish farming industry worldwide. In addition, because fish rely more heavily on their innate immune defences than mammals, they might constitute a potential rich source of antiviral compounds for fighting against mammalian viral infections.
      Full-text · Article · Sep 2009 · Mini Reviews in Medicinal Chemistry