Viral Pathogenesis and Novel Vaccines for Fish Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 September 2025) | Viewed by 4682

Special Issue Editor


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Guest Editor
Institute of Marine & Environmental Technology, University of Maryland, Baltimore, MD 21202, USA
Interests: molecular biology of aquatic RNA viruses; viral pathogenesis; virulence; reverse genetics; recombinant vaccines; oral vaccines

Special Issue Information

Dear Colleagues,

Many RNA viruses significantly impact the aquaculture industry, including infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia virus (VHSV), spring viremia of carp virus (SVCV), infectious pancreatic necrosis virus (IPNV), infectious salmon anemia virus (ISAV), salmonid alphavirus (SAV), piscine orthoreovirus (PRV), nervous necrosis virus (NNV), Tilapia lake virus (TiLV) and piscine myocarditis virus (PCMV). These viruses primarily affecting fish populations cause significant mortality rates and economic losses in aquaculture operations.

This Special Issue aims to cover the aspects of viral pathogenesis and virulence of these RNA viruses that constitute strategic targets for the development of novel vaccines. We accept original research and review articles about viral pathogenesis, molecular determinants of virulence, and the new generation of vaccines that include recombinant protein-based, nucleic acid-based, recombinant attenuated or virus vector-based (using reverse genetics) and nanoparticle-based oral vaccines against these RNA viruses.

Dr. Vikram Vakharia
Guest Editor

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Keywords

  • fish
  • RNA viruses
  • viral pathogenesis
  • virulence
  • reverse genetics
  • recombinant vaccines
  • oral vaccines

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Published Papers (4 papers)

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Research

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15 pages, 4623 KB  
Article
Putative Fusion-Associated Small Transmembrane (FAST) Proteins Encoded by Viruses of Pistolviridae, Order Ghabrivirales, Identified from In Silico Analyses
by Racheal Amono, Turhan Markussen, Øystein Evensen and Aase B. Mikalsen
Viruses 2026, 18(2), 193; https://doi.org/10.3390/v18020193 - 1 Feb 2026
Viewed by 635
Abstract
Fusion-associated small transmembrane (FAST) proteins are viral nonstructural proteins known to be encoded by specific members of the Spinareoviridae, specifically within the Aquareovirus and Orthoreovirus genera. These proteins specialize in mediating cell–cell fusion, leading to syncytia. Unlike enveloped viruses, naked viruses do [...] Read more.
Fusion-associated small transmembrane (FAST) proteins are viral nonstructural proteins known to be encoded by specific members of the Spinareoviridae, specifically within the Aquareovirus and Orthoreovirus genera. These proteins specialize in mediating cell–cell fusion, leading to syncytia. Unlike enveloped viruses, naked viruses do not rely on fusion proteins for cell entry; however, such proteins may facilitate viral spread between cells. Although not essential for virus replication, FAST proteins have been shown to enhance viral replication, particularly during the early stages of infection. More recently, proteins with characteristics resembling FAST proteins have been identified in a broader range of viruses, including several rotavirus species within the family Sedoreoviridae, and, unexpectedly, in some enveloped viruses within the Coronaviridae family. Here, we present protein sequence analyses suggesting that viruses of the recently established virus family Pistolviridae (order Ghabrivirales) also encode proteins with similarity to FAST proteins. Pistolviruses are small double-stranded RNA viruses that infect piscine species, and were initially referred to as “toti-like” viruses due to genomic similarities with members of the former Totiviridae, which infect single-celled organisms. The putative FAST proteins of the pistolviruses may be expressed either from small, distinct open reading frames or suggested to be produced as cleavage products derived from polyproteins. Full article
(This article belongs to the Special Issue Viral Pathogenesis and Novel Vaccines for Fish Viruses)
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18 pages, 1223 KB  
Article
Dynamics of Tilapia Lake Virus in Recirculating Aquaculture Systems and the Impact of Vaccination on Outbreak Control
by Montakarn Sresung, Jidapa Yamkasem, Supitchaya Theplhar, Piyathip Setthawong, Surapong Rattanakul, Skorn Mongkolsuk, Kwanrawee Sirikanchana, Win Surachetpong and Tuchakorn Lertwanakarn
Viruses 2026, 18(1), 96; https://doi.org/10.3390/v18010096 - 9 Jan 2026
Cited by 1 | Viewed by 987
Abstract
Tilapia lake virus (TiLV) is a highly virulent pathogen that has caused substantial mortality in tilapia farms, particularly those with open-water systems. However, TiLV can also emerge and persist in closed environments, such as recirculating aquaculture systems (RAS), where environmental accumulation and repeated [...] Read more.
Tilapia lake virus (TiLV) is a highly virulent pathogen that has caused substantial mortality in tilapia farms, particularly those with open-water systems. However, TiLV can also emerge and persist in closed environments, such as recirculating aquaculture systems (RAS), where environmental accumulation and repeated exposure may intensify infection and sustain outbreaks. In this case study, we conducted three field experiments to better understand TiLV dynamics among Nile tilapia in RAS. In experiment I, we quantified the TiLV levels in the fish, water, and sediment to compare outbreak and no-outbreak conditions and found that the TiLV concentrations in liver samples and the water were significantly higher in the outbreak ponds and positively correlated with increased fish mortality. In experiment II, we used a side-by-side field trial to evaluate the protective efficacy of a TiLV vaccine and its effects on the viral loads in the fish and aquatic environment during outbreaks. The vaccinated fish showed substantially lower cumulative mortality (16.7%) than the unvaccinated controls (37.7%), with a relative percent survival of 55.6%. Additionally, the TiLV concentrations in the pond water of the vaccinated group were significantly lower. In experiment III, we compared the TiLV patterns between RAS and non-RAS operations to determine how water recirculation influences viral accumulation and outbreak severity. The results revealed limited viral accumulation and shorter disease outbreak duration in the non-RAS. Overall, our findings showed that the TiLV levels in the rearing water were closely linked with disease severity in the RAS-based tilapia hatcheries. Continuous water recirculation allowed the virus to build up in the system, which led to more prolonged outbreaks, while the non-RAS conditions with regular water discharge showed lower viral loads and faster recovery. The vaccinated fish had better survival rates and released less virus into the water, which helped reduce infection pressure across the ponds. Together, these results suggest that combining vaccination with good water management and molecular monitoring can provide a practical, noninvasive way to detect and control TiLV outbreaks in intensive farming systems. Full article
(This article belongs to the Special Issue Viral Pathogenesis and Novel Vaccines for Fish Viruses)
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19 pages, 2688 KB  
Article
Development of a Novel Virus-Like Particle-Based Vaccine Against PRV-1 Suitable for DIVA Strategies
by Claudia Galleguillos-Becerra, Matias Cardenas, Yesseny Vásquez-Martínez, Francisca Tapia, Zulema Yañez, Tomas Cancino, Iván Valdés and Marcelo Cortez-San Martín
Viruses 2025, 17(12), 1578; https://doi.org/10.3390/v17121578 - 2 Dec 2025
Cited by 1 | Viewed by 1279
Abstract
Piscine orthoreovirus genotype 1 (PRV-1) is an emerging viral pathogen in salmon aquaculture that causes Heart and Skeletal Muscle Inflammation (HSMI), with high prevalence in salmon-producing countries such as Chile. A significant obstacle in PRV-1 vaccine development is the inability to culture the [...] Read more.
Piscine orthoreovirus genotype 1 (PRV-1) is an emerging viral pathogen in salmon aquaculture that causes Heart and Skeletal Muscle Inflammation (HSMI), with high prevalence in salmon-producing countries such as Chile. A significant obstacle in PRV-1 vaccine development is the inability to culture the virus in vitro, which limits the scalability and production of traditional inactivated or DNA-based vaccine strategies. This study describes the development of a novel virus-like particle (VLP)-based vaccine against PRV-1. Recombinant VLP were produced by co-expressing the six structural proteins of PRV-1 (λ1, λ2, μ1, σ1, σ2, σ3) using a baculovirus-based expression system in insect cells. In addition, to enable differentiating infected from vaccinated animals (DIVA) strategies, the σ1 protein was modified by adding of a cmyc epitope tag. The results demonstrated that the native VLP vaccine (VLP6n) significantly reduced viral loads in Atlantic salmon challenged with PRV-1. Moreover, in rainbow trout, the cmyc-tagged VLP-like vaccine (VLP6c) elicited a specific antibody response against the cmyc epitope, allowing differentiation between vaccinated and naturally infected fish. Overall, this VLP-based vaccine platform represents a promising strategy for controlling PRV-1 prevalence in salmon-producing counties, supporting the implementation of serological surveillance programs. Full article
(This article belongs to the Special Issue Viral Pathogenesis and Novel Vaccines for Fish Viruses)
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Review

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21 pages, 3336 KB  
Review
Toward Effective Vaccines Against Piscine Orthoreovirus: Challenges and Current Strategies
by Daniela Espinoza and Andrea Rivas-Aravena
Viruses 2025, 17(10), 1372; https://doi.org/10.3390/v17101372 - 14 Oct 2025
Viewed by 1208
Abstract
Piscine orthoreovirus (PRV) is a globally distributed viral pathogen that causes heart and skeletal muscle inflammation (HSMI) in Atlantic salmon (Salmo salar) and affects other salmonids, yet no commercial vaccines are currently available. Major barriers to vaccine development include the inability [...] Read more.
Piscine orthoreovirus (PRV) is a globally distributed viral pathogen that causes heart and skeletal muscle inflammation (HSMI) in Atlantic salmon (Salmo salar) and affects other salmonids, yet no commercial vaccines are currently available. Major barriers to vaccine development include the inability to propagate PRV in cell lines and the low, variable immunogenicity of its proteins, particularly the outer capsid protein σ1, which mediates viral attachment. This protein is hypothesized to be immunologically relevant due to its homology with Mammalian orthoreoviruses. Recombinant σ1 expressed in conventional systems exhibits poor antibody recognition, whereas structural modifications such as lipidation or fusion with molecular chaperones improve epitope exposure. Formalin-inactivated vaccines have shown inconsistent protection, often failing to elicit robust innate or adaptive responses, especially under cohabitation challenge. In contrast, DNA vaccines encoding σ1 and the non-structural protein μNS have demonstrated partial efficacy, likely due to enhanced intracellular expression and antigen presentation. Nonetheless, the considerable variability observed in immune responses among individual fish and viral genotypes, together with suggestions that PRV may interfere with antiviral pathways, represent additional barriers to achieving consistent vaccine efficacy. This review summarizes the current status of PRV vaccine development and discusses future directions for rational design based on optimized antigens and intracellular delivery platforms. Full article
(This article belongs to the Special Issue Viral Pathogenesis and Novel Vaccines for Fish Viruses)
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