Reversion of molecularly engineered, partially attenuated, very virulent infectious bursal disease virus during infection of commercial chickens

Raue, R.; Islam, M. Rafiqul; Islam, Md. Kamrul; Badhy, SC; Das, Pabitra Chandra; Müller, Hermann

doi:10.1080/03079450310001652112

Cited by 36 publications

(26 citation statements)

References 42 publications

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“…In addition, the alteration of VP2 amino acids (aa) 253, 279, and/or 284 of a vvIBDV strain by reverse genetics conferred adaptation to chicken embryo fibroblasts (CEF) (32)(33)(34). The resulting viruses proved to be attenuated for chickens (34,35), but reversion mutations were observed upon passage in chickens and could restore virulence (36). VP2 is, however, unlikely to be the only factor for virulence: laboratory-engineered reassortant viruses derived from vvIBDV exhibited delayed replication in the bursa (37) or failed to induce morbidity and mortality (31) unless they also had a typical vvIBDV-related segment B.…”

Section: Nfectious Bursal Disease Virus (Ibdv) Of Chickens (Gallus mentioning

confidence: 99%

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

Escaffre

Nouën

Amelot

et al. 2013

J Virol

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f Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs.

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Section: Nfectious Bursal Disease Virus (Ibdv) Of Chickens (Gallus mentioning

confidence: 99%

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

Escaffre

Nouën

Amelot

et al. 2013

J Virol

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“…In addition to this strategy, Salmonella typhimurium and Shigella flexneri have been used to deliver plasmid DNA vaccines to elicit protective immune responses in mice [2,7]. In light of these successes, it should be noted that major safety concerns such as pathogenic reversion, horizontal gene transfer and adverse inflammatory responses with respect to using these approaches in human beings still exist [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Immunization with non-replicating E. coli minicells delivering both protein antigen and DNA protects mice from lethal challenge with lymphocytic choriomeningitis virus

Giacalone

Zapata

Berkley

et al. 2007

Vaccine

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In the midst of new investigations into the mechanisms of both delivery and protection of new vaccines and vaccine carriers, it has become clear that immunization with delivery mechanisms that do not involve living, replicating organisms are vastly preferred. In this report, non-replicating bacterial minicells simultaneously co-delivering the nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) and the corresponding DNA vaccine were tested for the ability to generate protective cellular immune responses in mice. It was found that good protection (89%) was achieved after intramuscular administration, moderate protection (31%) was achieved after intranasal administration, and less protection (7%) was achieved following gastric immunization. These results provide a solid foundation on which to pursue the use of bacterial minicells as a non-replicating vaccine delivery platform.

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“…Single point mutations in the capsids of poliovirus (65), murine norovirus (4), infectious bursal disease virus (64), and adenoassociated viruses (67) have all been demonstrated to have significant effects on both in vitro and in vivo growth characteristics of the viruses. Reversion of an attenuated phenotype to a pathogenic wild type has also been reported for many animal viruses, such as poliovirus (35), porcine reproductive and respiratory syndrome virus (48), and infectious bursal disease virus (54). In the current study, the F51L and T59A mutants are genetically stable in pigs, as the viruses recovered from the inoculated pigs over the course of infection all retained these two mutations.…”

Section: Vol 85 2011 Mutations Important For Hev Attenuation 5347mentioning

confidence: 65%

Three Amino Acid Mutations (F51L, T59A, and S390L) in the Capsid Protein of the Hepatitis E Virus Collectively Contribute to Virus Attenuation

Córdoba

Huang

Opriessnig

et al. 2011

J Virol

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Hepatitis E virus (HEV) is an important but extremely understudied human pathogen, and the mechanisms of HEV replication and pathogenesis are largely unknown. We previously identified an attenuated genotype 3 HEV mutant (pSHEV-1) containing three unique amino acid mutations (F51L, T59A, and S390L) in the capsid protein. To determine the role of each of these mutations, we constructed three HEV single mutants (rF51L, rT59A, and rS390L) which were all found to be replication competent in Huh7 liver cells. To determine the pathogenicities of the mutants, we utilized the specific-pathogen-free (SPF) pig model for HEV and a unique inoculation procedure that bypasses the need for propagating infectious HEV in vitro. A total of 60 pigs were intrahepatically inoculated, via an ultrasound-guided technique, with in vitro-transcribed full-length capped RNA transcripts from the infectious clones of each single mutant, the pSHEV-1 triple mutant, wild-type pSHEV-3, or phosphate-buffered saline (PBS) buffer (n ‫؍‬ 10). The results showed that the F51L mutation partially contributed to virus attenuation, whereas the T59A and S390L mutations resulted in more drastic attenuation of HEV in pigs, as evidenced by a significantly lower incidence of viremia, a delayed appearance and shorter duration of fecal virus shedding and viremia, and lower viral loads in liver, bile, and intestinal content collected at three different necropsy times. The results indicate that the three mutations in the capsid protein collectively contribute to HEV attenuation. This study has important implications for developing a modified live-attenuated vaccine against HEV.Hepatitis E virus (HEV) is a major cause of enterically transmitted acute hepatitis in many developing countries in Asia, the Middle East, and Africa and in Mexico (2,13,[40][41][42]49), although the disease has also been reported in many industrialized countries, including the United States (53). HEV is transmitted primarily by the fecal-oral route through contaminated drinking water or food. The disease generally affects young adults and has a mortality rate of less than 1% in the general population, although a significantly higher rate of mortality, up to 30%, has been reported in infected pregnant women (47). HEV is a small nonenveloped virus, and its genome is a single-strand, positive-sense RNA molecule of approximately 7.2 kb in size. Currently, HEV is classified in the genus Hepevirus of the family Hepeviridae (9).The genomic RNA of HEV contains a short 5Ј noncoding region (NCR), three open reading frames (ORF1, -2, and -3), and a 3Ј NCR (22). A cap structure has been identified at the 5Ј end of the viral genome and is required for efficient virus replication in vivo (14). The ORF2 and ORF3 proteins are translated from a bicistronic subgenomic mRNA (18,25). ORF1 encodes a nonstructural protein with multiple functional domains, including methyltransferase, papain-like protease, helicase, and RNA-dependent RNA polymerase (RdRp) (29). It remains unclear whether the ORF1 polyprotein func...

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Reversion of molecularly engineered, partially attenuated, very virulent infectious bursal disease virus during infection of commercial chickens

Cited by 36 publications

References 42 publications

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus

Immunization with non-replicating E. coli minicells delivering both protein antigen and DNA protects mice from lethal challenge with lymphocytic choriomeningitis virus

Three Amino Acid Mutations (F51L, T59A, and S390L) in the Capsid Protein of the Hepatitis E Virus Collectively Contribute to Virus Attenuation

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