Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine

Gladue, Douglas P.; Holinka, Lauren G.; Fernandez-Sainz, I.; Prarat, Melanie; O'Donell, V.; Vepkhvadze, N.; Lu, Zhiqiang; Rogers, Kara; Risatti, Guillermo R.

doi:10.1016/j.virol.2010.07.040

Cited by 34 publications

(40 citation statements)

References 62 publications

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“…This is reflected in numerous reports in which mutations of different functional domains in the structural proteins C, E rns , E1, and E2 and in the nonstructural proteins p7 and NS4B were shown to reduce the pathogenicity in pigs, indicating that these genes may be involved in determining CSFV virulence (7,8,9,10,11,12,13,32,36,37,38,39,40,46,54).…”

Section: Discussionmentioning

confidence: 98%

“…Comparison of the genomes of the GPE Ϫ vaccine virus and the parent ALD virus revealed 225 nucleotide substitutions and 46 amino acid differences (22), which did not provide any conclusive information on the molecular basis of the attenuation. Numerous reports suggest that the viral proteins N pro , C, E rns , E1, E2, p7, and NS4B may be involved in determining the virulence of CSFV in pigs (7,8,9,10,11,12,13,32,36,37,38,39,40,43,46,54). So far, however, all conclusions on CSFV virulence determinants rely on mutations that result in downregulation of pathogenicity.…”

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confidence: 99%

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Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

Tamura

Sakoda

Yoshino

et al. 2012

J Virol

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c Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), a highly contagious disease of pigs. There are numerous CSFV strains that differ in virulence, resulting in clinical disease with different degrees of severity. Low-virulent and moderately virulent isolates cause a mild and often chronic disease, while highly virulent isolates cause an acute and mostly lethal hemorrhagic fever. The live attenuated vaccine strain GPE ؊ was produced by multiple passages of the virulent ALD strain in cells of swine, bovine, and guinea pig origin. With the aim of identifying the determinants responsible for the attenuation, the GPE ؊ vaccine virus was readapted to pigs by serial passages of infected tonsil homogenates until prolonged viremia and typical signs of CSF were observed. The GPE ؊ /P-11 virus isolated from the tonsils after the 11th passage in vivo had acquired 3 amino acid substitutions in E2 (T830A) and NS4B (V2475A and A2563V) compared with the virus before passages. Experimental infection of pigs with the mutants reconstructed by reverse genetics confirmed that these amino acid substitutions were responsible for the acquisition of pathogenicity. Studies in vitro indicated that the substitution in E2 influenced virus spreading and that the changes in NS4B enhanced the viral RNA replication. In conclusion, the present study identified residues in E2 and NS4B of CSFV that can act synergistically to influence virus replication efficiency in vitro and pathogenicity in pigs.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

Tamura

Sakoda

Yoshino

et al. 2012

J Virol

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“…A porcine primary macrophage cDNA expression library was constructed (Clontech, Mountain View, CA) using monocytes/macrophages obtained from healthy CSFV-free swine exactly as previously described [19]. Macrophage cultures were prepared from defibrinated swine blood.…”

Section: Methodsmentioning

confidence: 99%

“…As ‘prey’, the previously described swine macrophage cDNA library and bovine cDNA library containing proteins fused to the GAL4 Activation Domain (AD) was used. Screening was done as previously described [19]. Sequencing of the identified library clones was performed by the dideoxynucleotide chain-termination method [23].…”

Section: Methodsmentioning

confidence: 99%

Interaction of CSFV E2 Protein with Swine Host Factors as Detected by Yeast Two-Hybrid System

et al. 2014

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E2 is one of the envelope glycoproteins of pestiviruses, including classical swine fever virus (CSFV) and bovine viral diarrhea virus (BVDV). E2 is involved in several critical functions, including virus entry into target cells, induction of a protective immune response and virulence in swine. However, there is no information regarding any host binding partners for the E2 proteins. Here, we utilized the yeast two-hybrid system and identified fifty-seven host proteins as positive binding partners which bound E2 from both CSFV and BVDV with the exception of two proteins that were found to be positive for binding only to CSFV E2. Alanine scanning of CSFV E2 demonstrated that the binding sites for these cellular proteins on E2 are likely non-linear binding sites. The possible roles of the identified host proteins are discussed as the results presented here will be important for future studies to elucidate mechanisms of host protein-virus interactions during pestivirus infection. However, due to the limitations of the yeast two hybrid system, the proteins identified is not exhaustive and each interaction identified needs to be confirmed by independent experimental approaches in the context of virus-infected cells before any definitive conclusion can be drawn on relevance for the virus life cycle.

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“…The C protein of CSFV influences the regulation of cellular transcription (5) and interacts with host SUMOylation proteins (6). The ability of the C protein to bind the cellular IQGAP1 protein during infection plays a critical role in determining the virulence of the virus (7).…”

mentioning

confidence: 99%

Hemoglobin Subunit Beta Interacts with the Capsid Protein and Antagonizes the Growth of Classical Swine Fever Virus

Hong

et al. 2013

J Virol

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The capsid (C) protein of the Flaviviridae family members is involved in nucleocapsid formation and virion assembly. However, the influence of C protein-interacting partners on the outcome of pestivirus infections is poorly defined. In this study, hemoglobin subunit beta (HB) was identified as a C protein-binding protein by glutathione S-transferase pulldown and subsequent mass spectrometry analysis of PK-15 cells, which are permissive cells for classical swine fever virus (CSFV). Coimmunoprecipitation and confocal microscopy confirmed that HB interacts and colocalizes with the C protein in the cytoplasm. Silencing of HB with small interfering RNAs promoted CSFV growth and replication, whereas overexpression of HB suppressed CSFV replication and growth. Interestingly, HB was found to interact with retinoic acid-inducible gene I and increase its expression, resulting in increased production of type I interferon (IFN). However, HB was unable to suppress CSFV growth when the RIG-I pathway was blocked. Overall, our results suggest that cellular HB antagonizes CSFV growth and replication by triggering IFN signaling, and might represent a novel antiviral restriction factor. This study reports for the first time the novel role of HB in innate immunity.

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Effects of the interactions of classical swine fever virus Core protein with proteins of the SUMOylation pathway on virulence in swine

Cited by 34 publications

References 62 publications

Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

Selection of Classical Swine Fever Virus with Enhanced Pathogenicity Reveals Synergistic Virulence Determinants in E2 and NS4B

Interaction of CSFV E2 Protein with Swine Host Factors as Detected by Yeast Two-Hybrid System

Hemoglobin Subunit Beta Interacts with the Capsid Protein and Antagonizes the Growth of Classical Swine Fever Virus

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