Infectious bursal disease virus is an icosahedral polyploid dsRNA virus

Department of Structure of Macromolecules, Centro Nacional de Biotecnología/CSIC, Cantoblanco, 28049 Madrid, Spain.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2009; 106(7):2148-52. DOI: 10.1073/pnas.0808498106
Source: PubMed


Viruses are a paradigm of the economy of genome resources, reflected in their multiplication strategy and for their own structure. Although there is enormous structural diversity, the viral genome is always enclosed within a proteinaceous coat, and most virus species are haploid; the only exception to this rule are the highly pleomorphic enveloped viruses. We performed an in-depth characterization of infectious bursal disease virus (IBDV), a non-enveloped icosahedral dsRNA virus with a bisegmented genome. Up to 6 natural populations can be purified, which share a similar protein composition but show higher sedimentation coefficients as particle density increases. Stoichiometry analysis of their genome indicated that these biophysical differences correlate with the copy number of dsRNA segments inside the viral capsid. This is a demonstration of a functional polyploid icosahedral dsRNA virus. We show that IBDV particles with greater genome copy number have higher infectivity rates. Our results show an unprecedented replicative strategy for dsRNA viruses and suggest that birnaviruses are living viral entities encompassing numerous functional and structural characteristics of positive and negative ssRNA viruses.

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Available from: Daniel Luque, Jan 08, 2014
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    • "Poultry producers around the globe suffer significant economic losses inflicted by infectious bursal disease (IBD), which is a highly immunosuppressive viral disease of chickens. The IBD virus (IBDV) belongs to the family Birnaviridae and has a polyploid , bisegmented genome which enables the virus to reassort under field conditions [19]. The virus has predilection for lymphoid tissues especially the bursa of Fabricius (BF). "
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    ABSTRACT: Infectious bursal disease (IBD) is a highly contagious disease of chickens which leads to immunosuppression. In our previous study it was demonstrated that, possibly, CD4+ and CD8+ T cells may employ perforin and granzyme-A pathway for the clearance of IBDV-infected bursal cells. In this study, we evaluated the cytotoxic T cell responses involving two independently functioning but complementary mechanisms: Fas–Fas ligand and perforin–granzyme pathways in IBDV-infected chickens. As demonstrated previously, infection of chickens with IBDV was accompanied by influx of CD8+ T cells in the bursa and spleen. There was an upregulation in the gene expression of cytolytic molecules: Fas and Fas ligand (FasL), perforin (PFN) and granzyme-A (Gzm-A) in bursal and in the splenic tissues of IBDV inoculated chickens. Additionally, for the first time, we detected Fas, Fas ligand, Caspase-3 and PFN producing CD8+ T cells in the bursa and spleen of IBDV-infected chickens. The infiltration and activation of CD8+ T cells was substantiated by the detection of Th1 cytokine, IFN-γ. These data suggest that T cells may be involved in the clearance of virus from the target organ bursa and peripheral tissues such as spleen. The findings of these studies provide new insights into the pathogenesis of IBD and provide mechanistic evidence that the cytotoxic T cells may act through both Fas–FasL and perforin–granzyme pathways in mediating the clearance of virus-infected cells.
    Results in Immunology 12/2012; 2:112–119. DOI:10.1016/j.rinim.2012.05.003
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    • "Indeed, the precise mechanism by which VP2 expression triggers PKR phosphorylation deserves an in depth characterization. VP3 is the second major structural IBDV protein [64]. This polypeptide is released simultaneously with pVP2 and the VP4 protease following the autocatalytic processing of the IBDV polyprotein [18]. "
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    ABSTRACT: Infectious bursal disease virus (IBDV) is an avian pathogen responsible for an acute immunosuppressive disease that causes major losses to the poultry industry. Despite having a bipartite dsRNA genome, IBDV, as well as other members of the Birnaviridae family, possesses a single capsid layer formed by trimers of the VP2 capsid protein. The capsid encloses a ribonucleoprotein complex formed by the genome associated to the RNA-dependent RNA polymerase and the RNA-binding polypeptide VP3. A previous report evidenced that expression of the mature VP2 IBDV capsid polypeptide triggers a swift programmed cell death response in a wide variety of cell lines. The mechanism(s) underlying this effect remained unknown. Here, we show that VP2 expression in HeLa cells activates the double-stranded RNA (dsRNA)-dependent protein kinase (PKR), which in turn triggers the phosphorylation of the eukaryotic initiation factor 2α (eIF2α). This results in a strong blockade of protein synthesis and the activation of an apoptotic response which is efficiently blocked by coexpression of a dominant negative PKR polypeptide. Our results demonstrate that coexpression of the VP3 polypeptide precludes phosphorylation of both PKR and eIF2α and the onset of programmed cell death induced by VP2 expression. A mutation blocking the capacity of VP3 to bind dsRNA also abolishes its capacity to prevent PKR activation and apoptosis. Further experiments showed that VP3 functionally replaces the host-range vaccinia virus (VACV) E3 protein, thus allowing the E3 deficient VACV deletion mutant WRΔE3L to grow in non-permissive cell lines. According to results presented here, VP3 can be categorized along with other well characterized proteins such us VACV E3, avian reovirus sigmaA, and influenza virus NS1 as a virus-encoded dsRNA-binding polypeptide with antiapoptotic properties. Our results suggest that VP3 plays a central role in ensuring the viability of the IBDV replication cycle by preventing programmed cell death.
    PLoS ONE 10/2012; 7(10):e46768. DOI:10.1371/journal.pone.0046768 · 3.23 Impact Factor
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    • "IPNV is responsible for an acute systemic disease affecting different species of freshwater and marine fishes, mollusks, and crustaceans [49]. Birnaviruses contain a polyploid bipartite dsRNA genome that is packaged into a single virus particle [50]. Structural units are derived from a polyprotein precursor that is translationally self-cleaved to release three polypeptides, pVP2 (the capsid protein precursor), VP4 (the protease) and VP3 [51]. "
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    ABSTRACT: RNA silencing is directly involved in antiviral defense in a wide variety of eukaryotic organisms, including plants, fungi, invertebrates, and presumably vertebrate animals. The study of RNA silencing-mediated antiviral defences in vertebrates is hampered by the overlap with other antiviral mechanisms; thus, heterologous systems are often used to study the interplay between RNA silencing and vertebrate-infecting viruses. In this report we show that the VP3 protein of the avian birnavirus Infectious bursal disease virus (IBDV) displays, in addition to its capacity to bind long double-stranded RNA, the ability to interact with double-stranded small RNA molecules. We also demonstrate that IBDV VP3 prevents the silencing mediated degradation of a reporter mRNA, and that this silencing suppression activity depends on its RNA binding ability. Furthermore, we find that the anti-silencing activity of IBDV VP3 is shared with the homologous proteins expressed by both insect- and fish-infecting birnaviruses. Finally, we show that IBDV VP3 can functionally replace the well-characterized HCPro silencing suppressor of Plum pox virus, a potyvirus that is unable to infect plants in the absence of an active silencing suppressor. Altogether, our results support the idea that VP3 protects the viral genome from host sentinels, including those of the RNA silencing machinery.
    PLoS ONE 09/2012; 7(9):e45957. DOI:10.1371/journal.pone.0045957 · 3.23 Impact Factor
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