Special Issue: Viruses Infecting Fish, Amphibians, and Reptiles

Although viruses infecting and affecting humans are the focus of considerable research effort, viruses that target other animal species, including cold-blooded vertebrates, are receiving increased attention. In part this reflects the interests of comparative virologists, but increasingly it is based on the impact that many viruses have on ecologically and commercially important animals. Frogs and other amphibians are sentinels of environmental health and their disappearance following viral or fungal (chytrid) infection is a cause for alarm. Likewise, because aquaculture and mariculture are providing an increasingly large percentage of the “seafood” consumed by humans, viral agents that adversely impact the harvest of cultured fish and amphibians are of equal concern. [...

Introduction: History and Future of Ranaviruses

Dr. Allan Granoff (1923–2012), who isolated the first ranavirus (Granoff et al. 1966), had, scattered throughout his office at St. Jude Children’s Research Hospital, a variety of frog-related items including the poem cited above. Although one of Allan’s isolates, Frog virus 3 (FV3), subsequently became the best-characterized member of both the genus (Ranavirus) and the family (Iridoviridae); the impact of that discovery was not fully appreciated at the time. FV3 was neither the first iridoviridae to be recognized as a pathogen of lower vertebrates or the first isolated. Those honors belonged to lymphocystis disease virus (LCDV) and Invertebrate iridovirus 1 (IIV1), respectively (Wissenberg 1965; Xeros 1954). LCDV is responsible for a generally non-life threatening, but disfiguring, disease in fish characterized by the appearance of wart-like growths on the skin and (rarely) internal organs, whereas IIV1 is the causative agent of latent and patent infections in crane fly larvae. Despite its lack of primacy, FV3 was studied because, in keeping with the mission of St. Jude Hospital, it was initially thought to be linked to adenocarcinoma in frogs and thus could be a useful model of human malignancies. Furthermore, unlike LCDV and IIV1, it could be readily grown in cultured cells and was thus amenable to detailed molecular characterization. Although its role in tumor development was soon proven incorrect, FV3 served as a gateway into understanding the replication strategy of a heretofore poorly studied virus family. Moreover, over the next 20 years, its study led to important insights not only into iridoviridae replication, but also eukaryotic biology, virus evolution, and host–virus interactions

Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR

<p>Abstract</p> <p>Background</p> <p>Ranaviruses (family <it>Iridoviridae</it>) are important pathogens of lower vertebrates. However, little is known about how they circumvent the immune response of their hosts. Many ranaviruses contain a predicted protein, designated vIF2α, which shows homology with the eukaryotic translation initiation factor 2α. In analogy to distantly related proteins found in poxviruses vIF2α might act as an inhibitor of the antiviral protein kinase PKR.</p> <p>Results</p> <p>We have characterized the function of vIF2α from <it>Rana catesbeiana </it>virus Z (RCV-Z). Multiple sequence alignments and secondary structure prediction revealed homology of vIF2α with eIF2α throughout the S1-, helical- and C-terminal domains. Genetic and biochemical analyses showed that vIF2α blocked the toxic effects of human and zebrafish PKR in a heterologous yeast system. Rather than complementing eIF2α function, vIF2α acted in a manner comparable to the vaccinia virus (VACV) K3L protein (K3), a pseudosubstrate inhibitor of PKR. Both vIF2α and K3 inhibited human PKR-mediated eIF2α phosphorylation, but not PKR autophosphorylation on Thr446. In contrast the E3L protein (E3), another poxvirus inhibitor of PKR, inhibited both Thr446 and eIF2α Ser51 phosphorylation. Interestingly, phosphorylation of eIF2α by zebrafish PKR was inhibited by vIF2α and E3, but not by K3. Effective inhibition of PKR activity coincided with increased PKR expression levels, indicative of relieved autoinhibition of PKR expression. Experiments with vIF2α deletion constructs, showed that both the N-terminal and helical domains were sufficient for inhibition of PKR, whereas the C-terminal domain was dispensable.</p> <p>Conclusions</p> <p>Our results show that RCV-Z vIF2α is a functional inhibitor of human and zebrafish PKR, and probably functions in similar fashion as VACV K3. This constitutes an important step in understanding the interaction of ranaviruses and the host innate immune system.</p

THIRD INTERNATIONAL SYMPOSIUM ON RANAVIRUSES:: ADVANCING THE UNDERSTANDING OF THE THREAT OF RANAVIRUSES TO NORTH AMERICAN HERPETOFAUNA

Members of the genus Ranavirus, one of five genera withinthe family Iridoviridae, encompass a group of large, doublestrandedDNA viruses that infect all three classes of ectothermicvertebrates: fish, amphibians, and reptiles. Ranaviruses areglobally emerging pathogens that cause considerable morbidityand mortality among diverse populations. In North America,ranavirus epizootics are regularly reported in wild and culturedfish, amphibian, and reptile populations

The Molecular Biology of Frog Virus 3 and other Iridoviruses Infecting Cold-Blooded Vertebrates

Frog virus 3 (FV3) is the best characterized member of the family Iridoviridae. FV3 study has provided insights into the replication of other family members, and has served as a model of viral transcription, genome replication, and virus-mediated host-shutoff. Although the broad outlines of FV3 replication have been elucidated, the precise roles of most viral proteins remain unknown. Current studies using knock down (KD) mediated by antisense morpholino oligonucleotides (asMO) and small, interfering RNAs (siRNA), knock out (KO) following replacement of the targeted gene with a selectable marker by homologous recombination, ectopic viral gene expression, and recombinant viral proteins have enabled researchers to systematically ascertain replicative- and virulence-related gene functions. In addition, the application of molecular tools to ecological studies is providing novel ways for field biologists to identify potential pathogens, quantify infections, and trace the evolution of ecologically important viral species. In this review, we summarize current studies using not only FV3, but also other iridoviruses infecting ectotherms. As described below, general principles ascertained using FV3 served as a model for the family, and studies utilizing other ranaviruses and megalocytiviruses have confirmed and extended our understanding of iridovirus replication. Collectively, these and future efforts will elucidate molecular events in viral replication, intrinsic and extrinsic factors that contribute to disease outbreaks, and the role of the host immune system in protection from disease

ICTV Virus Taxonomy Profile: Iridoviridae

The Iridoviridae is a family of large, icosahedral viruses with double-stranded DNA genomes ranging in size from 103 to 220 kbp. Members of the subfamily Alphairidovirinae infect ectothermic vertebrates (bony fish, amphibians and reptiles), whereas members of the subfamily Betairidovirinae mainly infect insects and crustaceans. Infections can be either covert or patent, and in vertebrates they can lead to high levels of mortality among commercially and ecologically important fish and amphibians. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Iridoviridae, which is available at www.ictv.global/report/iridoviridae.</p

Molecular and Ecological Studies of a Virus Family (Iridoviridae) Infecting Invertebrates and Ectothermic Vertebrates

Research involving viruses within the family Iridoviridae (generically designated iridovirids to distinguish members of the family Iridoviridae from members of the genus Iridovirus) has markedly increased in recent years [...

Molecular basis of pathogenesis of emerging viruses infecting aquatic animals

Aquatic vertebrates are very abundant in the world, and they are of tremendous importance in providing global food security and nutrition. However, emergent and resurgent viruses, such as ranavirus (e.g., Rana grylio virus, RGV and Andriasd avidianus ranavirus, ADRV), herpesvirus (e.g., Carassius carassius herpesvirus, CaHV), reovirus (e.g., grass carp reovirus 109, GCRV-109, Scophthal musmaximus reovirus, SMReV and Micropterus salmoides reovirus, MsReV), and rhabdovirus (e.g., Siniper cachuatsi rhabdovirus, SCRV and Scophthal musmaximus rhabdovirus, SMRV) can cause severe diseases in aquaculture animals and wild lower vertebrates, such as frogs, giant salamanders, fish, and so on. Here, we will briefly describe the symptoms produced by the aforementioned viruses and the molecular basis of the virus–host interactions. This manuscript aims to provide an overview of viral diseases in lower vertebrates with an emphasis on visible symptomatic manifestations and pathogenesis