scholarly journals The Full Region of N-Terminal in Polymerase of IBDV Plays an Important Role in Viral Replication and Pathogenicity: Either Partial Region or Single Amino Acid V4I Substitution Does Not Completely Lead to the Virus Attenuation to Three-Yellow Chickens

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 107
Author(s):  
Weiwei Wang ◽  
Yu Huang ◽  
Zhonghua Ji ◽  
Guo Chen ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Reverse Genetics ◽  
Histopathological Examination ◽  
Infectious Bursal Disease ◽  
Single Amino Acid ◽  
Effective Prevention ◽  
Partial Region ◽  
Terminal Domain ◽  
Bursal Disease

Infectious Bursal Disease Virus (IBDV) has haunted the poultry industry with severe, prolonged immunosuppression of chickens when infected at an early age and can easily lead to other secondary infections. Understanding the pathogenic mechanisms could lead to effective prevention and control of Infectious Bursal Disease (IBD). Evidence suggests that the N-terminal domain of polymerase in segment B plays an important role, but it is not clear which part or residual is crucial for the pathogenicity. Using a reverse genetics technique, a molecular clone (rNN1172) of the parental vvIBDV strain NN1172 was generated, and its pathogenicity was found to be the same as the parental virus. Then, three recombinant chimeric viruses were rescued based on the rNN1172 and substituted with the counterparts in the N-terminal domain of the attenuated vaccine strain B87: the rNN1172-B87VP1a (substituting the full region of the 1–167 aa residuals), the rNN1172-B87VP1a∆4 (substituting the region of the 5–167 aa residuals), and the rNN1172-VP1∆4 (one single aa residual substitution V4I), to better explore the role of the N-terminal domain of polymerase on the viral pathogenicity. Interestingly, all these substitutions played different roles in the viral pathogenicity: the mortality of the rNN1172-B87VP1a-challenged chickens was significantly reduced from 30% to 0%. No obvious lesion was found in the histopathological examination, and the lowest viral genome copy number was also detected in the bursa when compared to the parental and two other recombinant viruses. The mortalities caused by rNN1172-B87VP1a∆4 and rNN1172-B87VP1∆4, respectively, were all reduced to 10% and had a delayed onset of death. Our results also revealed that the pathogenicity of the IBDV was consistent with the viral replication efficiency in vivo (bursae). This study demonstrated that the full region of the N-terminal of polymerase plays an important role in viral replication and pathogenicity, but the substitutions of its partial region or a single residual do not completely lead to the virus attenuation to Three-Yellow chickens, although that significantly reduces its pathogenicity.

scholarly journals VP5 and the N terminus of VP2 are not responsible for the different pathotype of serotype I and II infectious bursal disease virus

2001 ◽  
Vol 82 (1) ◽  
pp. 159-169 ◽  
Author(s):  
Anja Schröder ◽  
Adriaan A. W. M. van Loon ◽  
Danny Goovaerts ◽  
Jens Peter Teifke ◽  
Egbert Mundt
Keyword(s):  
B Lymphocytes ◽  
Disease Virus ◽  
Infectious Bursal Disease Virus ◽  
Reverse Genetics ◽  
Bursa Of Fabricius ◽  
Infectious Bursal Disease ◽  
Bursal Disease ◽  
Chimeric Viruses

Two serotypes have been identified in infectious bursal disease virus (IBDV), a member of the family Birnaviridae. A reverse genetics system was used for generation of chimeras in genome segment A of the two serotypes, in which the complete viral VP5 gene and 3′ noncoding region (NCR), or parts thereof, were exchanged. The engineered viruses were characterized in vitro and in vivo in comparison to serotype I and II IBDV. Our results show that IBDV chimeras exhibit a different phenotype in cell culture compared to the wild-type viruses. In in vitro-cultivated bursal-derived cells, chimeric viruses infected B lymphocytes, as does serotype I IBDV. Surprisingly, serotype II virus was also able to infect in vitro-cultivated bursal cells, but these were neither B lymphocytes nor macrophages. After infection of susceptible chickens all chimeras replicated in the bursa of Fabricius (BF), and three chimeric viruses caused mild depletion of bursal cells. In contrast, after infection of chickens with a chimeric IBDV containing exchanged VP5 as well as 3′-NCR, no depletion was detectable. The serotype II strain did not replicate in the BF nor did it cause depletion of bursal cells. Thus, the origin of VP5 does not explain the different pathotype of IBDV serotype I and II.

scholarly journals TRIM25 inhibits infectious bursal disease virus replication by targeting VP3 for ubiquitination and degradation

2021 ◽  
Vol 17 (9) ◽  
pp. e1009900
Author(s):  
Suyan Wang ◽  
Mengmeng Yu ◽  
Aijing Liu ◽  
Yuanling Bao ◽  
Xiaole Qi ◽  
...  
Keyword(s):  
Viral Replication ◽  
Disease Virus ◽  
Infectious Bursal Disease Virus ◽  
Defense Responses ◽  
Immune Defense ◽  
Infectious Bursal Disease ◽  
Structural Protein ◽  
Bursal Disease

Infectious bursal disease virus (IBDV), a double-stranded RNA virus, causes immunosuppression and high mortality in 3–6-week-old chickens. Innate immune defense is a physical barrier to restrict viral replication. After viral infection, the host shows crucial defense responses, such as stimulation of antiviral effectors to restrict viral replication. Here, we conducted RNA-seq in avian cells infected by IBDV and identified TRIM25 as a host restriction factor. Specifically, TRIM25 deficiency dramatically increased viral yields, whereas overexpression of TRIM25 significantly inhibited IBDV replication. Immunoprecipitation assays indicated that TRIM25 only interacted with VP3 among all viral proteins, mediating its K27-linked polyubiquitination and subsequent proteasomal degradation. Moreover, the Lys854 residue of VP3 was identified as the key target site for the ubiquitination catalyzed by TRIM25. The ubiquitination site destroyed enhanced the replication ability of IBDV in vitro and in vivo. These findings demonstrated that TRIM25 inhibited IBDV replication by specifically ubiquitinating and degrading the structural protein VP3.

scholarly journals Transcriptomic Analysis of Inbred Chicken Lines Reveals Infectious Bursal Disease Severity Is Associated with Greater Bursal Inflammation In Vivo and More Rapid Induction of Pro-Inflammatory Responses in Primary Bursal Cells Stimulated Ex Vivo

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 933
Author(s):  
Amin S. Asfor ◽  
Salik Nazki ◽  
Vishwanatha R.A.P. Reddy ◽  
Elle Campbell ◽  
Katherine L. Dulwich ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Severe Disease ◽  
Infectious Bursal Disease ◽  
Rna Seq ◽  
Rapid Induction ◽  
Cytoskeletal Regulation ◽  
Bursal Disease

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p < 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.

scholarly journals Transcriptomic analysis reveals that severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses in primary bursal cells stimulated ex vivo.

2021 ◽  
Author(s):  
Amin S Asfor ◽  
Salik Nazki ◽  
Vishwanatha RAP Reddy ◽  
Elle Campbell ◽  
Katherine L Dulwich ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Severe Disease ◽  
Infectious Bursal Disease ◽  
White Leghorn ◽  
Rapid Induction ◽  
Cytoskeletal Regulation ◽  
Bursal Disease

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p<0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.

scholarly journals Nuclear Factor NF45 Interacts with Viral Proteins of Infectious Bursal Disease Virus and Inhibits Viral Replication

2010 ◽  
Vol 84 (20) ◽  
pp. 10592-10605 ◽  
Author(s):  
Ruth L. O. Stricker ◽  
Sven-Erik Behrens ◽  
Egbert Mundt
Keyword(s):  
Viral Replication ◽  
Disease Virus ◽  
Infectious Bursal Disease Virus ◽  
Molecular Mechanisms ◽  
Viral Proteins ◽  
Infectious Bursal Disease ◽  
Nuclear Factor ◽  
Replication Process ◽  
Bursal Disease ◽  
Infected Cells

ABSTRACT Two of the central issues in developing new strategies to interfere with viral infections concern the identification of cellular proteins involved in viral replication and/or antiviral measures and the dissection of the underlying molecular mechanisms. To gain initial insight into the role of host proteins in the life cycle of infectious bursal disease virus (IBDV), a double-stranded RNA virus, we examined the cellular nuclear factor 45 (NF45). NF45 was previously indicated to be involved in the replication process of other types of RNA viruses. Interestingly, by performing immunofluorescence studies, we found that in IBDV-infected cells the mainly nuclear NF45 accumulated at the sites of viral replication in the cytoplasm. NF45 was shown to specifically colocalize with the viral RNA-dependent RNA polymerase VP1, the capsid protein VP2, and the ribonucleoprotein VP3. Immunoprecipitation experiments indicated protein-protein associations between NF45 and VP1, VP2, and VP3. Expression of the individual VP3 or the combination of expression of VP1 and VP3 did not result in a cytoplasmic accumulation of NF45, which, among other data, showed that recruitment of the cellular protein in infected cells functionally correlates with the viral replication process. Since small interfering RNA(siRNA)-mediated downregulation of NF45 resulted in an approximately 5-fold increase of virus yield, our study suggests that NF45, by association with viral proteins, is part of a yet-uncharacterized cellular defense mechanism against IBDV infections.

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