Search Results (8)

Spring viremia of carp virus (SVCV) is a significant pathogen that has notably hindered the advancement of cyprinid aquaculture in recent years. Infections caused by SVCV are often associated with substantial economic losses due to the absence of effective treatment options. Previous reports indicated that N-(4-methyl-2-oxo-2H-chromen-7-yl) benzenesulfonamide (N6) exhibits inhibitory effects on SVCV proliferation. This study aims to comprehensively evaluate the anti-SVCV effects of N6 using healthy young carp as the experimental model. The research investigates the antiviral activity of this compound in vivo, the immune response of interferon (IFN)-related genes, its impact on the horizontal transmission of SVCV, and histopathological changes. The results indicate that N6 significantly inhibits SVCV infectivity and apoptosis in EPC cells in vitro. Furthermore, while N6 reduced horizontal transmission of SVCV in a static cohabitation challenge model, the N6-treated SVCV-infected group showed a nearly 3-fold decrease in viral load compared to the control group, it did not completely prevent transmission at established antiviral dosages. Histopathological analysis of the affected fish revealed that N6 effectively mitigated tissue damage induced by SVCV. Additionally, the up-regulation of six IFN-related genes suggests that N6 may indirectly activate IFNs to facilitate the clearance of SVCV in the kidney and spleen, as demonstrated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). These findings provide a foundation for further investigations into the mechanisms by which N6 acts against SVCV and may aid in the development of novel anti-SVCV therapeutics. Full article

Viperin is an interferon-stimulated gene (ISG) that plays an important role in the congenital antiviral immunity of vertebrates. In this study, the common carp viperin (cc-viperin) gene is characterized, and we determine whether it has the ability to inhibit spring viremia of carp virus (SVCV) replication in EPC cells. The results showed that the full-length cDNA of the cc-viperin gene was 1044 bp and it encoded 348 amino acids. The cc-viperin sequence contained a leucine zipper in the N-terminal, a CxxxCxxC motif in the SAM domain, and a conservative C-terminus. The cc-viperin gene’s nucleotide and amino acid sequence alignment revealed that cc-viperin displayed relatively high sequence identity compared with other species. Phylogenetic analysis displayed the close relation of cc-viperin with Carassius auratus and Mylopharyngodon piceus. Subcellular localization analysis indicated that the cc-viperin protein was located in the cytoplasm. The gene expression results showed that cc-viperin was expressed in all of the tissues tested. Its expression level significantly increased in EPC cells after 24 h to 72 h compared to the control during SVCV infection. Moreover, cc-viperin significantly inhibited SVCV replication when it was overexpressed, whereas it increased SVCV replication when it had reduced expression in EPC cells, respectively. To summarize, the results obtained in this work show that cc-viperin shares similar sequence characteristics with other vertebrates, and it could inhibit SVCV replication in EPC cells, displaying an antiviral effect in common carp. Full article

Spring viremia of carp virus (SVCV) is a rhabdovirus that primarily infects cyprinid finfishes and causes a disease notifiable to the World Organization for Animal Health. Amphibians, which are sympatric with cyprinids in freshwater ecosystems, are considered non-permissive hosts of rhabdoviruses. The potential host range expansion of SVCV in an atypical host species was evaluated by testing the susceptibility of amphibians native to the Pacific Northwest. Larval long-toed salamanders Ambystoma macrodactylum and Pacific tree frog Pseudacris regilla tadpoles were exposed to SVCV strains from genotypes Ia, Ib, Ic, or Id by either intraperitoneal injection, immersion, or cohabitation with virus-infected koi Cyprinus rubrofuscus. Cumulative mortality was 100% for salamanders injected with SVCV, 98–100% for tadpoles exposed to virus via immersion, and 0–100% for tadpoles cohabited with SVCV-infected koi. Many of the animals that died exhibited clinical signs of disease and SVCV RNA was found by in situ hybridization in tissue sections of immersion-exposed tadpoles, particularly in the cells of the gastrointestinal tract and liver. SVCV was also detected by plaque assay and RT-qPCR testing in both amphibian species regardless of the virus exposure method, and viable virus was detected up to 28 days after initial exposure. Recovery of infectious virus from naïve tadpoles cohabited with SVCV-infected koi further demonstrated that SVCV transmission can occur between classes of ectothermic vertebrates. Collectively, these results indicated that SVCV, a fish rhabdovirus, can be transmitted to and cause lethal disease in two amphibian species. Therefore, members of all five of the major vertebrate groups (mammals, birds, reptiles, fish, and amphibians) appear to be vulnerable to rhabdovirus infections. Future research studying potential spillover and spillback infections of aquatic rhabdoviruses between foreign and domestic amphibian and fish species will provide insights into the stressors driving novel interclass virus transmission events. Full article

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immune enhancement and immunosuppression activities, but the main role is immunosuppression and anti-inflammatory ability. In order to use the immunosuppressive function of IL-10, many viruses, such as SARS-CoV-2, hepatitis B virus and EB virus, can evade the host’s immune surveillance and clearance by increasing the expression of host IL-10. However, it has not been reported whether the aquatic animal infection virus can upregulate the expression of host IL-10 and the mechanisms are still unknown. Spring viremia of carp (SVC) is a fatal viral disease for many fish species and is caused by spring viremia of carp virus (SVCV). This disease has caused significant economic losses in the aquaculture industry worldwide. In this study, the expression of carp IL-10 with or without infection of SVCV in epithelioma papulosum cyprinid (EPC) cells, carp head kidney (cHK) primary cells and common carp tissues were analyzed using RT-PCR and ELISA. The results show that SVCV infection induced carp IL-10 mRNA and protein expression, both in vitro and in vivo. However, the upregulation of carp IL-10 by SVCV was hindered by specific inhibitors of the JAK inhibitor (CP-690550), STAT3 inhibitor (STA-21), NF-κB inhibitor (BAY11-7082) and p38 MAPK (mitogen-activated protein kinase) inhibitor (SB202190), but not JNK inhibitor (SP600125). Furthermore, the results demonstrated that JAK1, JAK2, JAK3, TYK2 and STAT5 played important roles in carp IL-10 production induced by SVCV infection. Taken together, SVCV infection significantly induced carp IL-10 expression and the upregulation trigged in JAK-STAT, NF-κB and p38MAPK pathways. To our knowledge, this is the first time that a fish infection virus upregulated the host IL-10 expression through the JAK-STAT, NF-κB and p38MAPK pathways. Altogether, fish viruses may have a similar mechanism as human or other mammalian viruses to escape host immune surveillance and clearance. Full article

In humans, four small HERCs (HERC3-6) exhibit differential degrees of antiviral activity toward HIV-1. Recently we revealed a novel member HERC7 of small HERCs exclusively in non-mammalian vertebrates and varied copies of herc7 genes in distinct fish species, raising a question of what is the exact role for a certain fish herc7 gene. Here, a total of four herc7 genes (named HERC7a–d sequentially) are identified in the zebrafish genome. They are transcriptionally induced by a viral infection, and detailed promoter analyses indicate that zebrafish herc7c is a typical interferon (IFN)-stimulated gene. Overexpression of zebrafish HERC7c promotes SVCV (spring viremia of carp virus) replication in fish cells and concomitantly downregulates cellular IFN response. Mechanistically, zebrafish HERC7c targets STING, MAVS, and IRF7 for protein degradation, thus impairing cellular IFN response. Whereas the recently-identified crucian carp HERC7 has an E3 ligase activity for the conjugation of both ubiquitin and ISG15, zebrafish HERC7c only displays the potential to transfer ubiquitin. Considering the necessity for timely regulation of IFN expression during viral infection, these results together suggest that zebrafish HERC7c is a negative regulator of fish IFN antiviral response. Full article

Immersion and intraperitoneal injection are the two most common methods used for the vaccination of fish. Because both methods require that fish are handled and thereby stressed, oral administration of vaccines as feed supplements is desirable. In addition, in terms of revaccination (boosting) of adult fish held in net pens, oral administration of vaccines is probably the only feasible method to obtain proper protection against diseases over long periods of time. Oral vaccination is considered a suitable method for mass immunization of large and stress-sensitive fish populations. Moreover, oral vaccines may preferably induce mucosal immunity, which is especially important to fish. Experimental oral vaccine formulations include both non-encapsulated and encapsulated antigens, viruses and bacteria. To develop an effective oral vaccine, the desired antigens must be protected against the harsh environments in the stomach and gut so they can remain intact when they reach the lower gut/intestine where they normally are absorbed and transported to immune cells. The most commonly used encapsulation method is the use of alginate microspheres that can effectively deliver vaccines to the intestine without degradation. Other encapsulation methods include chitosan encapsulation, poly D,L-lactide-co-glycolic acid and liposome encapsulation. Only a few commercial oral vaccines are available on the market, including those against infectious pancreatic necrosis virus (IPNV), Spring viremia carp virus (SVCV), infectious salmon anaemia virus (ISAV) and Piscirickettsia salmonis. This review highlights recent developments of oral vaccination in teleost fish. Full article

The PTEN (phosphatase and TENsin homolog on chromosome 10) gene encodes a bifunctional phosphatase that acts as a tumor suppressor. However, PTEN has been implicated in different immune processes, including autophagy, inflammation, regulation of natural killer (NK) cell cytolytic activity and type I interferon responses. Unlike mammals, zebrafish possess two pten genes (ptena and ptenb). This study explores the involvement of both zebrafish pten genes in antiviral defense. Although ptena^−/− and ptenb^−/− larvae were more susceptible to Spring viremia of carp virus (SVCV), the viral replication rate was lower in the mutant larvae than in the wild-type larvae. We observed that both mutant lines showed alterations in the transcription of numerous genes, including those related to the type I interferon (IFN) system, cytolytic activity, autophagy and inflammation, and some of these genes were regulated in opposite ways depending on which pten gene was mutated. Even though the lower replication rate of SVCV could be associated with impaired autophagy in the mutant lines, the higher mortality observed in the ptena^−/− and ptenb^−/− larvae does not seem to be associated with an uncontrolled inflammatory response. Full article

Global health is under attack by increasingly-frequent pandemics of viral origin. Antimicrobial peptides are a valuable tool to combat pathogenic microorganisms. Previous studies from our group have shown that the membrane-lytic region of turbot (Scophthalmus maximus) NK-lysine short peptide (Nkl_71–100) exerts an anti-protozoal activity, probably due to membrane rupture. In addition, NK-lysine protein is highly expressed in zebrafish in response to viral infections. In this work several biophysical methods, such as vesicle aggregation, leakage and fluorescence anisotropy, are employed to investigate the interaction of Nkl_71–100 with different glycerophospholipid vesicles. At acidic pH, Nkl_71–100 preferably interacts with phosphatidylserine (PS), disrupts PS membranes, and allows the content leakage from vesicles. Furthermore, Nkl_71–100 exerts strong antiviral activity against spring viremia of carp virus (SVCV) by inhibiting not only the binding of viral particles to host cells, but also the fusion of virus and cell membranes, which requires a low pH context. Such antiviral activity seems to be related to the important role that PS plays in these steps of the replication cycle of SVCV, a feature that is shared by other families of virus-comprising members with health and veterinary relevance. Consequently, Nkl_71–100 is shown as a promising broad-spectrum antiviral candidate. Full article