In vivo interference by Newcastle disease virus in chickens, the natural host of the virus

1989 ◽  
Vol 108 (3-4) ◽  
pp. 229-245 ◽  
Author(s):  
X. Li ◽  
R. P. Hanson
2008 ◽  
Vol 83 (2) ◽  
pp. 584-597 ◽  
Author(s):  
Elena Carnero ◽  
Wenjing Li ◽  
Antonio V. Borderia ◽  
Bruno Moltedo ◽  
Thomas Moran ◽  
...  

ABSTRACT One attractive strategy for the development of a human immunodeficiency virus (HIV) vaccine is the use of viral vectors with a proven safety profile and an absence of preexisting immunity in humans, such as Newcastle disease virus (NDV). Several NDV vaccine vectors have been generated, and their immunogenicities have been investigated with different animal models. However, a systematic study to evaluate the optimal insertion site of the foreign antigens into NDV that results in enhanced immune responses specific to the antigen has not yet been conducted. In this article, we describe the ability of NDV expressing HIV Gag to generate a Gag-specific immune response in mice. We also have determined the optimal insertion site into the NDV genome by generating recombinant NDV-HIVGag viruses in which HIV gag was located at different transcriptional positions throughout the NDV viral genome. All recombinant viruses were viable, grew to similar titers in embryonated chicken eggs, and expressed Gag in a stable manner. Our in vivo experiments revealed that higher HIV Gag protein expression positively correlates with an enhanced CD8+ T-cell-mediated immune response and protective immunity against challenge with vaccinia virus expressing HIV Gag. We also inserted a codon-optimized version of HIV gag in the described best location, between the P and M genes. Virus expressing the codon-optimized version of HIV gag induced a higher expression of the protein and an enhanced immune response against HIV Gag in mice. These results indicate that strategies directed toward increasing antigen expression by NDV result in enhanced immunogenicity and vaccine efficacy.


2004 ◽  
Vol 17 (4) ◽  
pp. 543-547 ◽  
Author(s):  
I. K. Park ◽  
H. L. Jiang ◽  
C. H. Yun ◽  
Y. J. Choi ◽  
S. J. Kim ◽  
...  

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Yanlong Jiang ◽  
Xing Gao ◽  
Ke Xu ◽  
Jianzhong Wang ◽  
Haibin Huang ◽  
...  

ABSTRACTMinicircle DNA (mcDNA), which contains only the necessary components for eukaryotic expression and is thus smaller than traditional plasmids, has been designed for application in genetic manipulation. In this study, we constructed a novel plasmid containing both the Cre recombinase under the phosphoglycerate kinase (PGK) promoter and recombinantlox66andlox71sites located outside the cytomegalovirus (CMV) expression cassette. The strictly controlled synthesis of Cre recombinasein vivomaintained the complete form of the plasmidin vitro, whereas thein vivoproduction of Cre transformed the parental plasmid to mcDNA after transfection. The newly designedCrerecombinase-mediatedin vivomcDNA platform, named CRIM, significantly increased the nuclear entry of mcDNA, followed by increased production of mRNA and protein, using enhanced green fluorescent protein (EGFP) as a model. Similar results were also observed in chickens when the vaccine was delivered by the regulated-delayed-lysisSalmonellastrain χ11218, where significantly increased production of EGFP was observed in chicken livers. Then, we used the HN gene of genotype VII Newcastle disease virus as an antigen model to construct the traditional plasmid pYL43 and the novel mcDNA plasmid pYL47. After immunization, our CRIM vaccine provided significantly increased protection against challenge compared with that of the traditional plasmid, providing us with a novel mcDNA vaccine platform.IMPORTANCEMinicircle DNA (mcDNA) has been considered an attractive alternative to DNA vaccines; however, the relatively high cost and complicated process of purifying mcDNA dramatically restricts the application of mcDNA in the veterinary field. We designed a novelin vivomcDNA platform in which the complete plasmid could spontaneously transform into mcDNAin vivo. In combination with the regulated-delayed-lysisSalmonellastrain, the newly designed mcDNA vaccine provides us with an elegant platform for veterinary vaccine development.


2009 ◽  
Vol 83 (11) ◽  
pp. 5943-5946 ◽  
Author(s):  
Yongqi Yan ◽  
Subrat N. Rout ◽  
Shin-Hee Kim ◽  
Siba K. Samal

ABSTRACT To determine the role of untranslated regions (UTRs) in replication and pathogenesis of Newcastle disease virus (NDV), we generated recombinant viruses with deletions in 5′ and 3′ UTRs of the HN mRNA. Deletion of any HN UTR did not noticeably affect in vitro replication of these viruses. However, complete deletion of the 5′ UTR of the HN gene decreased the HN mRNA levels and HN protein contents in virus particles, resulting in attenuation of the virus in chickens. This indicates that the 5′ UTR of HN mRNA plays an important role in replication and pathogenicity of NDV in vivo.


Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1249
Author(s):  
Archana Jadhav ◽  
Lele Zhao ◽  
Alice Ledda ◽  
Weiwei Liu ◽  
Chan Ding ◽  
...  

The expression of accessory non-structural proteins V and W in Newcastle disease virus (NDV) infections depends on RNA editing. These proteins are derived from frameshifts of the sequence coding for the P protein via co-transcriptional insertion of one or two guanines in the mRNA. However, a larger number of guanines can be inserted with lower frequencies. We analysed data from deep RNA sequencing of samples from in vitro and in vivo NDV infections to uncover the patterns of mRNA editing in NDV. The distribution of insertions is well described by a simple Markov model of polymerase stuttering, providing strong quantitative confirmation of the molecular process hypothesised by Kolakofsky and collaborators three decades ago. Our results suggest that the probability that the NDV polymerase would stutter is about 0.45 initially, and 0.3 for further subsequent insertions. The latter probability is approximately independent of the number of previous insertions, the host cell, and viral strain. However, in LaSota infections, we also observe deviations from the predicted V/W ratio of about 3:1 according to this model, which could be attributed to deviations from this stuttering model or to further mechanisms downregulating the abundance of W protein.


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