Local and systemic replicative fitness for viruses in specialist, generalist, and non-specialist interactions with salmonid hosts.

Host tissues represent diverse resources or barriers for pathogen replicative fitness. We tested whether viruses in specialist, generalist, and non-specialist interactions replicate differently in local entry tissue (fin), and systemic target tissue (kidney) using infectious hematopoietic necrosis virus (IHNV) and three salmonid fish hosts. Virus tissue replication was host specific, but one feature was shared by specialists and the generalist which was uncommon in the non-specialist interactions: high host entry and replication capacity in the local tissue after contact. Moreover, specialists showed increased replication in systemic target tissues early after host contact. By comparing ancestral and derived IHNV viruses, we also characterized replication tradeoffs associated with specialist and generalist evolution. Compared with the ancestral virus, a derived specialist gained early local replicative fitness in the new host but lost replicative fitness in the ancestral host. By contrast, a derived generalist showed small replication losses relative to the ancestral virus in the ancestral host but increased early replication in the local tissue of novel hosts. This study shows that the mechanisms of specialism and generalism are host specific and that local and systemic replication can contribute differently to overall within host replicative fitness for specialist and generalist viruses.

ICTV Virus Taxonomy Profile: Sunviridae 2023.

Sunviridae is a family of negative-sense RNA viruses with genomes of about 17.2 kb that have been found in snakes. The sunvirid genome comprises nonsegmented RNA with six open reading frames (ORFs) >1 kb that are predicted to encode six proteins. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Sunviridae, which is available at ictv.global/report/sunviridae.

Virus shedding kinetics and unconventional virulence tradeoffs.

Tradeoff theory, which postulates that virulence provides both transmission costs and benefits for pathogens, has become widely adopted by the scientific community. Although theoretical literature exploring virulence-tradeoffs is vast, empirical studies validating various assumptions still remain sparse. In particular, truncation of transmission duration as a cost of virulence has been difficult to quantify with robust controlled in vivo studies. We sought to fill this knowledge gap by investigating how transmission rate and duration were associated with virulence for infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss). Using host mortality to quantify virulence and viral shedding to quantify transmission, we found that IHNV did not conform to classical tradeoff theory. More virulent genotypes of the virus were found to have longer transmission durations due to lower recovery rates of infected hosts, but the relationship was not saturating as assumed by tradeoff theory. Furthermore, the impact of host mortality on limiting transmission duration was minimal and greatly outweighed by recovery. Transmission rate differences between high and low virulence genotypes were also small and inconsistent. Ultimately, more virulent genotypes were found to have the overall fitness advantage, and there was no apparent constraint on the evolution of increased virulence for IHNV. However, using a mathematical model parameterized with experimental data, it was found that host culling resurrected the virulence tradeoff and provided low virulence genotypes with the advantage. Human-induced or natural culling, as well as host population fragmentation, may be some of the mechanisms by which virulence diversity is maintained in nature. This work highlights the importance of considering non-classical virulence tradeoffs.

Characterization of maternal immunity following vaccination of broodstock against IHNV or Flavobacterium psychrophilum in rainbow trout (Oncorhynchusmykiss).

Infectious hematopoietic necrosis (IHN) is a significant viral disease affecting salmonids, whereas Flavobacterium psychrophilum (Fp), the causative agent of bacterial coldwater disease (BCWD), remains one of the most significant bacterial pathogens of salmonids. We explored maternal immunity in the context of IHN and BCWD management in rainbow trout (Oncorhynchus mykiss) aquaculture. Two experimental trials were conducted where different groups of female broodstock were immunized prior to spawning with an IHNV DNA vaccine or a live attenuated F. psychrophilum (Fp B.17-ILM) vaccine alone, or in combination. Progeny were challenged with either a low or high dose of IHNV at 13 days post hatch (dph) and 32 dph or challenged with F. psychrophilum at 13 dph. Mortality following a low-dose IHNV challenge at 13 dph was significantly lower in progeny from vaccinated broodstock vs. unvaccinated broodstock, but no significant differences were observed at 32 dph. Mortality due to BCWD was also significantly reduced in 13 dph fry that originated from broodstock immunized with the Fp B.17-ILM vaccine. After vaccination broodstock developed specific or neutralizing antibodies respectively to F. psychrophilum and IHNV; however, antibody titers in eggs and fry were undetectable. In the eggs and fry mRNA transcripts of the complement components C3 and C5 were detected at much higher levels in progeny from vaccinated broodstock and showed a significantly increased and rapid response post-challenge compared with unvaccinated broodstock. After challenges pro-inflammatory cytokine expression was immediately and considerably elevated in the fry from vaccinated broodstock vs. unvaccinated broodstock, whereas adaptive immune genes were elevated to a lesser degree. Results suggest that maternal transfer of innate and adaptive factors at the transcript level occurred because development of lymphomyeloid organs is not complete in such young fry. In addition to documenting maternally derived immunity in teleosts, this study demonstrates that broodstock vaccination can confer some degree of protection to progeny against viral and bacterial pathogens.

Coproduction and modeling spatial contact networks prevent bias about infectious hematopoietic necrosis virus transmission for Snake River Basin salmonids.

Much remains unknown about variation in pathogen transmission across the geographic range of a free-ranging fish or animal species and about the influence of movement (associated with husbandry practices or animal behavior) on pathogen transmission. Salmonid hatcheries are an ideal system in which to study these processes. Salmonid hatcheries are managed for endangered species recovery, supplementation of threatened or at-risk fish stocks, support of fisheries, and ecosystem stability. Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus of significant concern to salmon aquaculture. Landscape IHNV transmission dynamics previously had been estimated only for salmonid hatcheries in the Lower Columbia River Basin (LCRB). The objectives of this study were to estimate IHNV transmission dynamics in a unique geographic region, the Snake River Basin (SRB), and to quantitatively estimate the effect of model coproduction on inference because previous assessments of coproduction have been qualitative. In contrast to the LCRB, the SRB has hatchery complexes consisting of a main hatchery and ≥1 satellite facility. Knowledge about hatchery complexes was held by a subset of project researchers but would not have been available to project modelers without coproduction. Project modelers generated and tested multiple versions of Bayesian susceptible-exposedinfected models to realistically represent the SRB and estimate the effect of coproduction. Models estimated the frequency of transmission routes, route-specific infection probabilities, and infection probabilities for combinations of salmonid hosts and IHNV lineages. Model results indicated that in the SRB, avoiding exposure to IHNV-positive adult salmonids is the most important action to prevent juvenile infections. Migrating adult salmonids exposed juvenile cohort-sites most frequently, and the infection probability was greatest following exposure to migrating adults. Without coproduction, the frequency of exposure by migrating adults would have been overestimated by 70 cohort-sites, and the infection probability following exposure to migrating adults would have been underestimated by∼0.09. The coproduced model had less uncertainty in the infection probability if no transmission route could be identified (Bayesian credible interval (BCI) width = 0.12) compared to the model without coproduction (BCI width = 0.34). Evidence for virus lineage MD specialization on steelhead and rainbow trout (both Oncorhynchus mykiss) was apparent without model coproduction. In the SRB, we found a greater probability of virus lineage UC infection in Chinook salmon (Oncorhynchus tshawytscha) compared to in O. mykiss, whereas in the LCRB, UC more clearly exhibited a generalist approach. Coproduction influenced estimates that depended on transmission routes, which operated differently at main hatcheries and satellite sites within hatchery complexes. Hatchery complexes are found outside of the SRB and are not specific to salmonid hatcheries alone. There is great potential for coproduction and modeling spatial contact networks to advance understanding about infectious disease transmission in complex production systems and surrounding free-ranging animal populations.

ICTV Virus Taxonomy Profile: Rhabdoviridae 2022.

The family Rhabdoviridae comprises viruses with negative-sense (-) RNA genomes of 10-16 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants or animals, including mammals, birds, reptiles, amphibians or fish, as well as arthropods, which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish or agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Rhabdoviridae, which is available at ictv.global/report/rhabdoviridae.

The Nucleoprotein and Phosphoprotein Are Major Determinants of the Virulence of Viral Hemorrhagic Septicemia Virus in Rainbow Trout.

Viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus, infects several marine and freshwater fish species. There are many strains of VHSV that affect different fish, but some strains of one genetic subgroup have gained high virulence in rainbow trout (Oncorhynchus mykiss). To define the genetic basis of high virulence in trout, we used reverse genetics to create chimeric VHSVs in which viral nucleoprotein (N), P (phosphoprotein), or M (matrix protein) genes, or the N and P genes, were exchanged between a trout-virulent European VHSV strain (DK-3592B) and a trout-avirulent North American VHSV strain (MI03). Testing of the chimeric recombinant VHSV (rVHSV) by intraperitoneal injection in juvenile rainbow trout showed that exchanges of the viral P or M genes had no effect on the trout virulence phenotype of either parental strain. However, reciprocal exchanges of the viral N gene resulted in a partial gain of function in the chimeric trout-avirulent strain (22% mortality) and complete loss of virulence for the chimeric trout-virulent strain (2% mortality). Reciprocal exchanges of both the N and P genes together resulted in complete gain of function in the chimeric avirulent strain (82% mortality), again with complete loss of virulence in the chimeric trout-virulent strain (0% mortality). Thus, the VHSV N gene contains an essential determinant of trout virulence that is strongly enhanced by the viral P gene. We hypothesize that the host-specific virulence mechanism may involve increased efficiency of the viral polymerase complex when the N and P proteins have adapted to more efficient interaction with a host component from rainbow trout.IMPORTANCE Rainbow trout farming is a major food source industry worldwide that has suffered great economic losses due to host jumps of fish rhabdovirus pathogens, followed by evolution of dramatic increases in trout-specific virulence. However, the genetic determinants of host jumps and increased virulence in rainbow trout are unknown for any fish rhabdovirus. Previous attempts to identify the viral genes containing trout virulence determinants of viral hemorrhagic septicemia virus (VHSV) have not been successful. We show here that, somewhat surprisingly, the viral nucleocapsid (N) and phosphoprotein (P) genes together contain the determinants responsible for trout virulence in VHSV. This suggests a novel host-specific virulence mechanism involving the viral polymerase and a host component. This differs from the known virulence mechanisms of mammalian rhabdoviruses based on the viral P or M (matrix) protein.

ICTV Virus Taxonomy Profile: Paramyxoviridae.

The family Paramyxoviridae consists of large enveloped RNA viruses infecting mammals, birds, reptiles and fish. Many paramyxoviruses are host-specific and several, such as measles virus, mumps virus, Nipah virus, Hendra virus and several parainfluenza viruses, are pathogenic for humans. The transmission of paramyxoviruses is horizontal, mainly through airborne routes; no vectors are known. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the family Paramyxoviridae. which is available at ictv.global/report/paramyxoviridae.

Phylogeography and evolution of infectious hematopoietic necrosis virus in China.

Infectious hematopoietic necrosis virus (IHNV) is a well-known rhabdoviral pathogen of salmonid fish. In this study, a comprehensive analysis of 40 IHNV viruses isolated from thirteen fish farms in nine geographically dispersed Chinese provinces during 2012 to 2017 is presented. Identity of nucleotide and amino acid sequences among all the complete glycoprotein (G) genes from Chinese isolates was 98.0-100% and 96.7-100%, respectively. Coalescent phylogenetic analyses revealed that all the Chinese IHN virus characterized in this study were in a monophyletic clade that had a most recent common ancestor with the J Nagano (JN) subgroup within the J genogroup of IHNV. Within the Chinese IHNV clade isolates obtained over successive years from the same salmon fish farm clustered in strongly supported subclades, suggesting maintenance and diversification of virus over time within individual farms. There was also evidence for regional virus transmission within provinces, and some cases of longer distance transmission between distant provinces, such as Gansu and Yunnan. The data demonstrated that IHNV has evolved into a new subgroup in salmon farm environments in China, and IHNV isolates are undergoing molecular evolution within fish farms. We suggest that Chinese IHNV comprises a separate JC subgroup within the J genogroup of IHNV.

The glycoprotein, non-virion protein, and polymerase of viral hemorrhagic septicemia virus are not determinants of host-specific virulence in rainbow trout.

BACKGROUND: Viral hemorrhagic septicemia virus (VHSV), a fish rhabdovirus belonging to the Novirhabdovirus genus, causes severe disease and mortality in many marine and freshwater fish species worldwide. VHSV isolates are classified into four genotypes and each group is endemic to specific geographic regions in the north Atlantic and Pacific Oceans. Most viruses in the European VHSV genotype Ia are highly virulent for rainbow trout (Oncorhynchus mykiss), whereas, VHSV genotype IVb viruses from the Great Lakes region in the United States, which caused high mortality in wild freshwater fish species, are avirulent for trout. This study describes molecular characterization and construction of an infectious clone of the virulent VHSV-Ia strain DK-3592B from Denmark, and application of the clone in reverse genetics to investigate the role of selected VHSV protein(s) in host-specific virulence in rainbow trout (referred to as trout-virulence). METHODS: Overlapping cDNA fragments of the DK-3592B genome were cloned after RT-PCR amplification, and their DNA sequenced by the di-deoxy chain termination method. A full-length cDNA copy (pVHSVdk) of the DK-3592B strain genome was constructed by assembling six overlapping cDNA fragments by using natural or artificially created unique restriction sites in the overlapping regions of the clones. Using an existing clone of the trout-avirulent VHSV-IVb strain MI03 (pVHSVmi), eight chimeric VHSV clones were constructed in which the coding region(s) of the glycoprotein (G), non-virion protein (NV), G and NV, or G, NV and L (polymerase) genes together, were exchanged between the two clones. Ten recombinant VHSVs (rVHSVs) were generated, including two parental rVHSVs, by transfecting fish cells with ten individual full-length plasmid constructs along with supporting plasmids using the established protocol. Recovered rVHSVs were characterized for viability and growth in vitro and used to challenge groups of juvenile rainbow trout by intraperitoneal injection. RESULTS: Complete sequence of the VHSV DK-3592B genome was determined from the cloned cDNA and deposited in GenBank under the accession no. KC778774. The trout-virulent DK-3592B genome (genotype Ia) is 11,159 nt in length and differs from the trout-avirulent MI03 genome (pVHSVmi) by 13% at the nucleotide level. When the rVHSVs were assessed for the trout-virulence phenotype in vivo, the parental rVHSVdk and rVHSVmi were virulent and avirulent, respectively, as expected. Four chimeric rVHSVdk viruses with the substitutions of the G, NV, G and NV, or G, NV and L genes from the avirulent pVHSVmi constructs were still highly virulent (100% mortality), while the reciprocal four chimeric rVHSVmi viruses with genes from pVHSVdk remained avirulent (0-10% mortality). CONCLUSIONS: When chimeric rVHSVs, containing all the G, NV, and L gene substitutions, were tested in vivo, they did not exhibit any change in trout-virulence relative to the background clones. These results demonstrate that the G, NV and L genes of VHSV are not, by themselves or in combination, major determinants of host-specific virulence in trout.

Taxonomy of the order Mononegavirales: update 2019.

In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Taxonomy of the order Mononegavirales: second update 2018.

In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

ICTV Virus Taxonomy Profile: Rhabdoviridae.

The family Rhabdoviridae comprises viruses with negative-sense (-) single-stranded RNA genomes of 10.8-16.1 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants and animals including mammals, birds, reptiles and fish, as well as arthropods which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish and agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Rhabdoviridae, which is available at www.ictv.global/report/rhabdoviridae.

Molecular systematics of sturgeon nucleocytoplasmic large DNA viruses.

Namao virus (NV) is a sturgeon nucleocytoplasmic large DNA virus (sNCLDV) that can cause a lethal disease of the integumentary system in lake sturgeon Acipenser fulvescens. As a group, the sNCLDV have not been assigned to any currently recognized taxonomic family of viruses. In this study, a data set of NV DNA sequences was generated and assembled as two non-overlapping contigs of 306,448 bp and then used to conduct a comprehensive systematics analysis using Bayesian inference of phylogeny for NV, other sNCLDV and representative members of six families of the NCLDV superfamily. The phylogeny of NV was reconstructed using protein homologues encoded by nine nucleocytoplasmic virus orthologous genes (NCVOGs): NCVOG0022 - mcp, NCVOG0038 - DNA polymerase B elongation subunit, NCVOG0076 - VV A18-type helicase, NCVOG0249 - VV A32-type ATPase, NCVOG0262 - AL2 VLTF3-like transcription factor, NCVOG0271 - RNA polymerase II subunit II, NCVOG0274 - RNA polymerase II subunit I, NCVOG0276 - ribonucleotide reductase small subunit and NCVOG1117 - mRNA capping enzyme. The accuracy of our phylogenetic method was evaluated using a combination of Bayesian statistical analysis and congruence analysis. Stable tree topologies were obtained with data sets differing in target molecule(s), sequence length and taxa. Congruent topologies were obtained in phylogenies constructed using individual protein data sets. The major capsid protein phylogeny inferred that ten representative sNCLDV form a monophyletic group comprised of four lineages within a polyphyletic Mimi-Phycodnaviridae group of taxa. Overall, the analyses revealed that Namao virus is a member of the Mimiviridae family with strong and consistent support for a clade containing NV and CroV as sister taxa.

Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials.

Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted to convert all currently official names of species included in the virus family Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment. [Arenaviridae; binomials; ICTV; International Committee on Taxonomy of Viruses; Mononegavirales; virus nomenclature; virus taxonomy.].

Problems of classification in the family Paramyxoviridae.

A number of unassigned viruses in the family Paramyxoviridae need to be classified either as a new genus or placed into one of the seven genera currently recognized in this family. Furthermore, numerous new paramyxoviruses continue to be discovered. However, attempts at classification have highlighted the difficulties that arise by applying historic criteria or criteria based on sequence alone to the classification of the viruses in this family. While the recent taxonomic change that elevated the previous subfamily Pneumovirinae into a separate family Pneumoviridae is readily justified on the basis of RNA dependent -RNA polymerase (RdRp or L protein) sequence motifs, using RdRp sequence comparisons for assignment to lower level taxa raises problems that would require an overhaul of the current criteria for assignment into genera in the family Paramyxoviridae. Arbitrary cut off points to delineate genera and species would have to be set if classification was based on the amino acid sequence of the RdRp alone or on pairwise analysis of sequence complementarity (PASC) of all open reading frames (ORFs). While these cut-offs cannot be made consistent with the current classification in this family, resorting to genus-level demarcation criteria with additional input from the biological context may afford a way forward. Such criteria would reflect the increasingly dynamic nature of virus taxonomy even if it would require a complete revision of the current classification.

Taxonomy of the order Mononegavirales: update 2018.

In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.

ICTV Virus Taxonomy Profile: Pneumoviridae.

The family Pneumoviridae comprises large enveloped negative-sense RNA viruses. This taxon was formerly a subfamily within the Paramyxoviridae, but was reclassified in 2016 as a family with two genera, Orthopneumovirus and Metapneumovirus. Pneumoviruses infect a range of mammalian species, while some members of the Metapneumovirus genus may also infect birds. Some viruses are specific and pathogenic for humans, such as human respiratory syncytial virus and human metapneumovirus. There are no known vectors for pneumoviruses and transmission is thought to be primarily by aerosol droplets and contact. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Pneumoviridae, which is available at www.ictv.global/report/pneumoviridae.

Infectious hematopoietic necrosis virus virological and genetic surveillance 2000-2012.

Surveillance records of the acute RNA pathogen of Pacific salmonid fish infectious hematopoietic necrosis virus are combined for the first time to enable landscape-level ecological analyses and modeling. The study area is the freshwater ecosystems of the large Columbia River watershed in the U.S. states of Washington, Oregon, and Idaho, as well as coastal rivers in Washington and Oregon. The study period is 2000-2012, and records were contributed by all five resource management agencies that operate conservation hatcheries in the study area. Additional records from wild fish were collected from the National Wild Fish Health Survey, operated by the U.S. Fish and Wildlife Survey. After curation and normalization, the data set consists of 6766 records, representing 1146 sample sites and 15 different fish hosts. The virus was found in an average of 12.4% of records, and of these 66.2% also have viral genetic analysis available. This data set is used to conduct univariate ecological and epidemiological analyses and develop a novel hierarchical landscape transmission model for an aquatic pathogen.

Taxonomy of the order Mononegavirales: update 2017.

In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).