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The Ambystoma tigrinum virus (ATV) RNase III gene can modulate host PKR activation and interferon production.

ABSTRACT: The iridovirus RNase III gene is one of 26 conserved core genes among the family Iridoviridae. Initial studies suggest this viral protein functions to suppress RNA interference pathways that may attack viral RNA during infection. Therefore, to determine if the Ambystoma tigrinum virus (ATV) RNase III-like gene (ORF 25R) can modulate the host innate immune response fish and human cells ectopically expressing 25R were treated with polyI:C and monitored for interferon synthesis and phosphorylation of eIF2? and PKR. We found a decrease in cellular IFN production and modulation of the PKR pathway. In addition, ATV deleted of the RNase III gene (ATV?25R) shows reduced pathogenicity in tiger salamanders. Collectively our data suggest that the ATV 25R protein is a pathogenesis factor that may function to help evade the host's immune response by masking activators of the IFN pathway.

SUBMITTER: Allen AG

PROVIDER: S-EPMC5623656 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The Ambystoma tigrinum virus (ATV) RNase III gene can modulate host PKR activation and interferon production.

Allen Alexander G AG Morgans Scott S Smith Eric E Aron Mariah M MM Jancovich James K JK

Virology 20170823

The iridovirus RNase III gene is one of 26 conserved core genes among the family Iridoviridae. Initial studies suggest this viral protein functions to suppress RNA interference pathways that may attack viral RNA during infection. Therefore, to determine if the Ambystoma tigrinum virus (ATV) RNase III-like gene (ORF 25R) can modulate the host innate immune response fish and human cells ectopically expressing 25R were treated with polyI:C and monitored for interferon synthesis and phosphorylation ...[more]

PMID: 28844332

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Project description:Hepatitis C virus is a poor inducer of interferon (IFN), although its structured viral RNA can bind the RNA helicase RIG-I, and activate the IFN-induction pathway. Low IFN induction has been attributed to HCV NS3/4A protease-mediated cleavage of the mitochondria-adapter MAVS. Here, we have investigated the early events of IFN induction upon HCV infection, using the cell-cultured HCV JFH1 strain and the new HCV-permissive hepatoma-derived Huh7.25.CD81 cell subclone. These cells depend on ectopic expression of the RIG-I ubiquitinating enzyme TRIM25 to induce IFN through the RIG-I/MAVS pathway. We observed induction of IFN during the first 12 hrs of HCV infection, after which a decline occurred which was more abrupt at the protein than at the RNA level, revealing a novel HCV-mediated control of IFN induction at the level of translation. The cellular protein kinase PKR is an important regulator of translation, through the phosphorylation of its substrate the eIF2alpha initiation factor. A comparison of the expression of luciferase placed under the control of an eIF2alpha-dependent (IRES(EMCV)) or independent (IRES(HCV)) RNA showed a specific HCV-mediated inhibition of eIF2alpha-dependent translation. We demonstrated that HCV infection triggers the phosphorylation of both PKR and eIF2alpha at 12 and 15 hrs post-infection. PKR silencing, as well as treatment with PKR pharmacological inhibitors, restored IFN induction in JFH1-infected cells, at least until 18 hrs post-infection, at which time a decrease in IFN expression could be attributed to NS3/4A-mediated MAVS cleavage. Importantly, both PKR silencing and PKR inhibitors led to inhibition of HCV yields in cells that express functional RIG-I/MAVS. In conclusion, here we provide the first evidence that HCV uses PKR to restrain its ability to induce IFN through the RIG-I/MAVS pathway. This opens up new possibilities to assay PKR chemical inhibitors for their potential to boost innate immunity in HCV infection.

Project description:BackgroundLoss of pond habitat is catastrophic to aquatic larval amphibians, but even reduction in the amount of time a breeding site holds water (hydroperiod) can influence amphibian development and limit reproductive success. Using the landscape variation of a glacial valley in the Greater Yellowstone Ecosystem as the context for a natural experiment, we examined variation in growth pattern and life history of the salamander Ambystoma tigrinum melanostictum and determined how these developmental characteristics varied with hydroperiod over several summers.ResultsIn ponds that dried early in the season, maximum larval size was reduced relative to the sizes achieved in permanent ponds. Ephemeral ponds were associated with early metamorphosis at small body sizes, while permanent ponds facilitated longer larval periods and later metamorphosis. Paedomorphosis resulted from indefinite metamorphic postponement, and was identified only in the most permanent environments. Patterns of growth and allometry were similar between ponds with different hydroperiods, but considerable life history variation was derived from modulating the timing of and size at metamorphosis. Considering maximum rates of growth and inferring the minimum size at metamorphosis across 25 ponds over the course of three years, we calculated that hydroperiods longer than three months are necessary to support these populations through metamorphosis and/or reproductive maturity.ConclusionsLandscape heterogeneity fosters life history variation in this natural population. Modulation of the complex ambystomatid life cycle allows this species to survive in unpredictable environments, but current trends towards rapid pond drying will promote metamorphosis at smaller sizes and could eliminate the paedomorphic phenotype from this region. Metamorphosis at small size is has been linked to altered fitness traits, including reduced survival and fecundity. Thus, widespread environmental truncation of larval periods may lead to decreased population persistence. We found that the hydroperiods of many ponds in this region are now shorter than the developmental period required for larvae to reach the minimum size for metamorphosis; these locations serve as reproductive sinks that may be detrimental for persistence of the species in the region.

Project description:Animals live in heterogeneous environments must navigate in order to forage or capture food, defend territories, and locate mates. These heterogeneous environments have a variety of substrates that differ in their roughness, texture, and other properties, all of which may alter locomotor performance. Despite such natural variation in substrate, many studies on locomotion use noncompliant surfaces that either are unrepresentative of the range of substrates experienced by species or underestimate maximal locomotor capabilities. The goal of this study was to determine the role of forefeet and hindfeet on substrates with different properties during walking in a generalized sprawling tetrapod, the tiger salamander (Ambystoma tigrinum). Adult salamanders (n = 4, SVL = 11.2-14.6 cm) walked across level dry sand (DS), semi-soft plaster of Paris (PoP), wet sand (WS), and a hard, noncompliant surface (table)-substrates that vary in compliance. Trials were filmed in dorsal and anterior views. Videos were analyzed to determine the number of digits and surface area of each foot in contact with the substrate. The surface area of the forelimbs contacting the substrate was significantly greater on DS and PoP than on WS and the table. The surface area of the hindlimbs contacting the substrate was significantly greater on DS than on all other substrates. There were no significant differences in the time that the fore- or hindfeet were in contact with the substrate as determined by the number of digits. We conclude that salamanders modulate the use of their feet depending on the substrate, particularly on DS which is known to increase the mechanical work and energy expended during locomotion owing to the fluid nature of its loose particles. More studies are needed to test a wider range of substrates and to incorporate behavioral data from field studies to get a better understanding of how salamanders are affected by different substrates in their natural environment.

Dataset Information

The Ambystoma tigrinum virus (ATV) RNase III gene can modulate host PKR activation and interferon production.

Publications

The Ambystoma tigrinum virus (ATV) RNase III gene can modulate host PKR activation and interferon production.

Similar Datasets

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