Anti-nervous necrosis virus activity of the growth hormone releasing peptide-6, GHRP-6
This study investigated whether the synthetic hexapeptide Growth Hormone-Releasing Peptide-6 (GHRP-6), a ghrelin analog with known growth-promoting and immunomodulatory properties in fish, could protect against Nervous Necrosis Virus (NNV) — a pathogen that damages the central nervous system of many commercially farmed fish species. The researchers used two complementary approaches. In vitro, E11 fish cell lines were treated with GHRP-6 before and/or during NNV infection; treated cells showed higher survival rates, reduced viral genome replication, and lower production of infective viral particles compared to untreated controls. In vivo, European seabass (Dicentrarchus labrax) were given intraperitoneal injections of GHRP-6, which led to significant upregulation of immune-related genes — including TNF-α, RTP3, and IgM — in the head kidney and intestine. NNV replication in the brain was also lower in GHRP-6-treated fish than in controls, and the brain's antiviral immune response was modulated. The authors conclude that GHRP-6 shows potential as an antiviral agent for aquaculture disease prevention. Key limitations include that all experiments were conducted in fish (not humans) and the in vivo work lacked a full challenge trial design.
Why this grade: All experimental work was conducted in fish cell lines and European seabass in vivo, with no human subjects or clinical data, limiting evidence grade to animal-only.
Growth hormone-releasing peptide 6 (GHRP-6), is a six-amino acid synthetic peptide that acts as a ghrelin analog and has shown growth-promoting and immunomodulatory activities in several fish species. This study evaluates the effects of GHRP-6 against the infection with the nervous necrosis virus (NNV), an important pathogen affecting the central nervous system of a wide range of fish species, including European seabass (Dicentrarchus labrax). For the in vitro evaluation, E11 cells were treated with GHRP-6 before and/or during viral infection, resulting in higher cellular survival rates, lower viral genome replication, and lower production of infective viral particles compared with control cells. These results indicate that GHRP-6 protects E11 cells from the viral infection. In order to conduct the in vivo evaluation, European seabass specimens were intraperitoneally injected with GHRP-6, resulting in the significant upregulation of several immune genes, such as TNF-A, RTP3, and IgM, in head kidney and intestine. Furthermore, NNV replication was lower in the brain from GHRP-6 injected fish than in controls, and the brain antiviral immune response was clearly modulated in treated fish. These results support the potential of GHRP-6 as an antiviral compound that could contribute to prevent viral diseases in fish farms, a priority for the aquaculture industry.
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