Ecology of Viruses Infecting Ectothermic Vertebrates—The Impact of Ranavirus Infections on Amphibians

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.

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“…To illustrate the above, a schematic diagram of the viral replication cycle is shown in Figure 2. [54]. Used with permission.…”

Section: Late Events/cytoplasmic Phasementioning

confidence: 99%

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

Chinchar

Jancovich

2011

Viruses

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109

103

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“…Ranaviruses, which constitute a genus within the family Iridoviridae , are important pathogens of ectotherms and have been associated with massive die-offs of both wild and farmed populations of fish, frogs and salamanders in diverse areas of the world [ 2 - 5 ]. Ranaviruses are double-stranded DNA viruses with genomes ranging from 105 to 140 kb.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR

2011

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BackgroundRanaviruses (family Iridoviridae) 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.ResultsWe have characterized the function of vIF2α from Rana catesbeiana 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.ConclusionsOur 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.

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“…Ranaviruses are emerging pathogens of fish, reptiles and amphibians that have caused mass host mortality in the Americas, Australia, Europe and Asia (Schock et al, 2008;Chinchar et al, 2009;Teacher, Cunningham & Garner, 2010;Chinchar, Robert & Storfer, 2011;Chinchar & Waltzek, 2014;Price et al, 2014Price et al, , 2017Rosa et al, 2017). Although ranavirosis has been reported for decades, lethal forms of the disease appear to be increasing in incidence and affecting new host populations (Gray, Miller & Hoverman, 2009;Price et al, 2014Price et al, , 2016, but impacts on host populations are inconsistent.…”

Section: Introductionmentioning

confidence: 99%

Sex‐biased disease dynamics increase extinction risk by impairing population recovery

Rosa

Bosch

Martel

et al. 2019

Animal Conservation

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The periodicity of life‐cycle events (phenology) modulates host availability to pathogens in a repeatable pattern. The effects of sexual differences in host phenology have been little explored in wildlife epidemiological studies. A recent series of ranavirosis outbreaks led to serious declines of Boscas’ newt populations at Serra da Estrela (Portugal). The peculiar phenology of this species, in which a large number of females remain in the aquatic habitat after the breeding season, turns it into a suitable model to test how sex‐biased mortality can affect host population persistence in the context of infectious diseases. We investigated how the phenology of Bosca's newt (i.e. biased number of females) mediated the impact of Ranavirus. We then evaluated the risk of extinction of the population under different scenarios of sex‐biased mortality using a population viability analysis. Two newt populations (one subject to yearly outbreaks and a comparative site where outbreaks have not been recorded) were tracked for trends over time following emergence of ranaviral disease, allowing us to assess the differential impact of the disease on both sexes. In addition to a significant decline in abundance of adult newts, our data suggest that phenology can affect disease dynamics indirectly, leading to reduction in females and a reversal of the sex ratio of the breeding population. Our models suggest that female‐biased mortality does not exacerbate Ranavirus‐driven population declines in the short‐term, but is likely to have a deleterious impact during the recovery process once the lethal effect of disease is removed from the system.

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Ecology of Viruses Infecting Ectothermic Vertebrates—The Impact of Ranavirus Infections on Amphibians

Cited by 9 publications

References 183 publications

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

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

Characterization of a ranavirus inhibitor of the antiviral protein kinase PKR

Sex‐biased disease dynamics increase extinction risk by impairing population recovery

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