An evolutionary divergent pestivirus lacking the Npro gene systemically infects a whale species.
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ABSTRACT:
SUBMITTER: Jo WK
PROVIDER: S-EPMC6758615 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atypical porcine pestivirus (APPV) is an emerging porcine virus that threatens global swine production. Pestiviruses can prevent interferon (IFN) production to avoid the host innate immune response, and the Npro viral protein can play a critical role. Knowledge of the host immune response to APPV infection is limited. Here, we showed that the IFN-β production was suppressed by APPV-Npro and the IFN regulatory factor 3 (IRF3) promoter activity stimulated by adaptor molecules of the IFN-β signaling pathway was also inhibited in the APPV-Npro-expressed cells. The APPV-Npro was able to interact with IRF3 and interfere the phosphorylation of IRF3, indicated that the IFN-β antagonism of APPV-Npro mainly depended on blocking IRF3 activity. To identify the functional region of APPV-Npro, a panel of truncated APPV-Npro was constructed, and its influence on the IRF3 activation was investigated. The results showed that the N-terminal 31-51 amino acids of APPV-Npro were mainly associated with inhibition of the IFN-β response. Taken together, this is the first study focusing on elucidating the function of APPV protein by revealing a novel mechanism of Npro in disruption of host IFN-β production, which will enlighten future study in addressing APPV pathogenesis and immune evasion.
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Project description:In higher vertebrates, phagocytosis plays a critical role in development and immunity, based on the internalization and removal of apoptotic cells and invading pathogens, respectively. Previous studies describe the effective uptake of these particles by lower vertebrate and invertebrate phagocytes, and identify important molecular players that contribute to this internalization. However, it remains unclear if individual phagocytes mediate internalization processes in these ancient organisms, and how this impacts the balance of pro-inflammatory and homeostatic events within their infection sites. Herein we show that individual phagocytes of the jawless vertebrate Petromyzon marinus (sea lamprey), like those of teleost fish and mice, display the capacity for divergent pro-inflammatory and homeostatic responses following internalization of zymosan and apoptotic cells, respectively. Professional phagocytes (macrophages, monocytes, neutrophils) were the primary contributors to the internalization of pro-inflammatory particles among goldfish (C. auratus) and lamprey (P. marinus) hematopoietic leukocytes. However, goldfish showed a greater ability for zymosan phagocytosis when compared to their jawless counterparts. Coupled to this increase was a significantly lower sensitivity of goldfish phagocytes to homeostatic signals derived from apoptotic cell internalization. Together, this translated into a significantly greater capacity for induction of antimicrobial respiratory burst responses compared to lamprey phagocytes, but also a decreased efficacy in apoptotic cell-driven leukocyte homeostatic mechanisms that attenuate this pro-inflammatory process. Overall, our results show the long-standing evolutionary contribution of intrinsic phagocyte mechanisms for the control of inflammation, and illustrate one effective evolutionary strategy for increased responsiveness against invading pathogens. In addition, they highlight the need for development of complementary regulatory mechanisms of inflammation to ensure continued maintenance of host integrity amidst increasing challenges from invading pathogens.
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Project description:Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was recently also described for the related pestiviruses, which are important livestock pathogens. HCV critically depends on the liver-specific miR-122, whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2) in the pestiviral 3’ untranslated region (UTR). Here, we elucidated the miRNA dependency of bovine viral diarrhea virus (BVDV) and confirmed its critical dependence on miR-17 and Argonaute 2 (AGO2). Let-7 binding to S1 had only minor effect on virus production but was required for full translational efficiency. Evolutionary selection experiments using seed site randomized genomes revealed that tropism could be re-directed to different miRNAs. AGO cross-linking and immunoprecipitation (AGO-CLIP) and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Furthermore, we identified variants with miRNA independent replication through acquisition of compensatory mutations near the genomic 3’ terminus. Rescue experiments using miRNA mimics demonstrated that miRNA binding and 3’ mutagenesis contribute to replication through mutually exclusive mechanisms. Our findings illustrate that pestiviruses, although capable of miRNA independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
2020-03-13 | GSE146910 | GEO
Project description:Pygmy right whale Evolutionary Genomics
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Project description:A novel pestivirus species was discovered in a piglet-producing farm in Austria during virologic examinations of congenital tremor cases. The emergence of this novel pestivirus species, provisionally termed Linda virus, in domestic pigs may have implications for classical swine fever virus surveillance and porcine health management.
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Project description:The genus Pestivirus, which belongs to the family Flaviviridae, includes ssRNA+ viruses responsible for infectious diseases in swine, cattle, sheep, goats, and other domestic and wild animals. Recently, several putative pestiviruses species have been discovered and characterized in mammalian species (giraffe pestivirus, antelope pestivirus, HoBi virus, Bungowannah virus, and Linda virus); one of these is a genetically distinct pestivirus, named atypical porcine pestivirus (APPV), discovered using the next-generation sequencing technology. APPV has been detected in piglets with congenital tremor (CT) from four different continents, including North America, South America, Europe, and Asia. There is strong evidence that experimental inoculation and in field outbreaks involving APPV induce CT in piglets. Additionally, splay leg (SL) syndrome has been observed concurrently with CT, and it was induced by APPV in experimental studies and some field cases. Animals with a persistent and/or chronic infection condition can shed the virus over time. Viral-RNA is frequently detected in different tissues from CT-piglets; however, high loads of APPV are detected most consistently in central nervous tissue. Moreover, the APPV genome has been recently detected in semen and preputial swabs from boar studs, as well as in serum and tissue samples from wild boars and domestic adult pigs, all known to be clinically healthy. Phylogenetic analysis revealed that the APPV sequence (complete or partial polyprotein) exhibits high genetic diversity between viral strains detected in different countries and formed independent clusters according to geographic location. Additional studies are needed to evaluate the molecular detection and sero-prevalence of APPV around the world. Lastly, more research is needed to understand clinical presentations associated with APPV infection, as well as the economic losses related to the virus in pig production worldwide.
| S-EPMC6393339 | biostudies-literature
Project description:Humpback whale song is an extraordinary example of vocal cultural behaviour. In northern populations, the complex songs show long-lasting traditions that slowly evolve, while in the South Pacific, periodic revolutions occur when songs are adopted from neighbouring populations and rapidly spread. In this species, vocal learning cannot be studied in the laboratory, learning is instead inferred from the songs' complexity and patterns of transmission. Here, we used individual-based cultural evolutionary simulations of the entire Southern and Northern Hemisphere humpback whale populations to formalize this process of inference. We modelled processes of song mutation and patterns of contact among populations and compared our model with patterns of song theme sharing measured in South Pacific populations. Low levels of mutation in combination with rare population interactions were sufficient to closely fit the pattern of diversity in the South Pacific, including the distinctive pattern of west-to-east revolutions. Interestingly, the same learning parameters that gave rise to revolutions in the Southern Hemisphere simulations gave rise to evolutionary patterns of cultural evolution in the Northern Hemisphere populations. Our study demonstrates how cultural evolutionary approaches can be used to make inferences about the learning processes underlying cultural transmission and how they might generate emergent population-level processes. This article is part of the theme issue 'Vocal learning in animals and humans'.
| S-EPMC8419575 | biostudies-literature
Project description:Host microRNA (miRNA) dependency is a hallmark of the human pathogen hepatitis C virus (HCV) and was also described for the related pestiviruses, which are important livestock pathogens. The liver-specific miR-122 binds within the HCV 5' untranslated region (UTR), whereas the broadly expressed let-7 and miR-17 families bind two sites (S1 and S2, respectively) in the pestiviral 3' UTR. Here, we dissected the mechanism of miRNA dependency of the pestivirus bovine viral diarrhea virus (BVDV). Argonaute 2 (AGO2) and miR-17 binding were essential for viral replication, whereas let-7 binding was mainly required for full translational efficiency. Furthermore, using seed site randomized genomes and evolutionary selection experiments, we found that tropism could be redirected to different miRNAs. AGO cross-linking and immunoprecipitation (CLIP) experiments and miRNA antagonism demonstrated that these alternative variants bound and depended on the corresponding miRNAs. Interestingly, we also identified miRNA-independent variants that were obtained through acquisition of compensatory mutations near the genomic 3' terminus. Rescue experiments demonstrated that miRNA binding and 3' mutagenesis contribute to replication through mutually exclusive mechanisms. Altogether, our findings suggest that pestiviruses, although capable of miRNA-independent replication, took advantage of miRNAs as essential host factors, suggesting a favorable path during evolutionary adaptation.
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Project description:The presence of congenital tremor (CT) type A-II in newborn piglets, caused by atypical porcine pestivirus (APPV), has been a focus since 2016. However, the source, evolutionary history, and transmission pattern of APPV in China remain poorly understood. In this study, we undertook phylogenetic analyses based on available complete E2 gene sequences along with 98 newly sequenced E2 genes between 2016 and 2020 in China within the context of global genetic diversity. The phylogenies revealed four distinct lineages of APPV, and interestingly, all lineages could be detected in China with the greatest diversity. Bayesian phylogenetic analyses showed that the E2 gene evolves at a mean rate of 1.22 × 10-3 (8.54 × 10-4-1.60 × 10-3) substitutions/site/year. The most recent common ancestor for APPVs is dated to 1886 (1837-1924) CE, somewhat earlier than the documented emergence of CT (1922 CE). Our phylogeographic analyses suggested that the APPV population possibly originated in the Netherlands, a country with developed livestock husbandry, and was introduced into China during the period 1837-2010. Guangdong, as a primary seeding population together with Central and Southwest China as epidemic linkers, was responsible for the dispersal of APPVs in China. The transmission pattern of "China lineages" (lineage 3 and lineage 4) presented a "south to north" movement tendency, which was likely associated with the implementation of strict environmental policy in China since 2000. Reconstruction of demographic history showed that APPV population size experienced multiple changes, which correlated well with the dynamic of the number of pigs in the past decades in China. Besides, positively selected pressure and geography-driven adaptation were supposed to be key factors for the diversification of APPV lineages. Our findings provide comprehensive insights into the diversity and spatiotemporal dynamic of APPV in China.
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Project description:Chapparvoviruses (ChPVs) comprise a divergent, recently identified group of parvoviruses (family Parvoviridae), associated with nephropathy in immunocompromised laboratory mice and with prevalence in deep sequencing results of livestock showing diarrhea. Here, we investigate the biological and evolutionary characteristics of ChPVs via comparative in silico analyses, incorporating sequences derived from endogenous parvoviral elements (EPVs) as well as exogenous parvoviruses. We show that ChPVs are an ancient lineage within the Parvoviridae, clustering separately from members of both currently established subfamilies. Consistent with this, they exhibit a number of characteristic features, including several putative auxiliary protein-encoding genes, and capsid proteins with no sequence-level homology to those of other parvoviruses. Homology modeling indicates the absence of a β-A strand, normally part of the luminal side of the parvoviral capsid protein core. Our findings demonstrate that the ChPV lineage infects an exceptionally broad range of host species, including both vertebrates and invertebrates. Furthermore, we observe that ChPVs found in fish are more closely related to those from invertebrates than they are to those of amniote vertebrates. This suggests that transmission between distantly related host species may have occurred in the past and that the Parvoviridae family can no longer be divided based on host affiliation.
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