scholarly journals Tissue tropism of recombinant coxsackieviruses in an adult mouse model

2005 ◽  
Vol 86 (7) ◽  
pp. 1897-1907 ◽  
Author(s):  
Heli Harvala ◽  
Hannu Kalimo ◽  
Jeffrey Bergelson ◽  
Glyn Stanway ◽  
Timo Hyypiä
Keyword(s):  
Neutralizing Antibodies ◽  
Plaque Assay ◽  
Tissue Tropism ◽  
Structural Protein ◽  
Coding Region ◽  
Protein Coding ◽  
Recombinant Viruses ◽  
Adult Mice ◽  
The Central Nervous System ◽  
Structural Region

Recombinant viruses, constructed by exchanging the 5′ non-coding region (5′NCR), structural and non-structural protein coding sequences were used to investigate determinants responsible for differences between coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) infections in adult mice and two cell lines. Plaque assay titration of recombinant and parental viruses from different tissues from adult BALB/c mice demonstrated that the structural region of CBV3 determined tropism to the liver tissue due to receptor recognition, and the 5′NCR of CBV3 enhanced viral multiplication in the mouse pancreas. Infection with a chimeric virus, containing the structural region from CBV3 and the rest of the genome from CAV9, and the parental CBV3 strain, caused high levels of viraemia in adult mice. The ability of these viruses to infect the central nervous system suggested that neurotropism is associated with high replication levels and the presence of the CBV3 capsid proteins, which also enhanced formation of neutralizing antibodies. Moreover, the appearance of neutralizing antibodies correlated directly with the clearance of the viruses from the tissues. These results demonstrate potential pathogenicity of intraspecies recombinant coxsackieviruses, and the complexity of the genetic determinants underlying tissue tropism.

scholarly journals Mapping of tissue tropism determinants in coxsackievirus genomes

2002 ◽  
Vol 83 (7) ◽  
pp. 1697-1706 ◽  
Author(s):  
Heli Harvala ◽  
Hannu Kalimo ◽  
Leif Dahllund ◽  
Juhana Santti ◽  
Pamela Hughes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Striated Muscle ◽  
Tissue Tropism ◽  
Cdna Clones ◽  
Coding Region ◽  
Newborn Mice ◽  
Recombinant Viruses ◽  
The Central Nervous System ◽  
Tissue Tropisms

Genomic regions responsible for the different tissue tropisms of coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) in newborn mice were investigated using recombinant viruses. Infectious cDNA clones of CAV9, a virus known to infect striated muscle, and CBV3, affecting the central nervous system, pancreas, liver, brown fat and striated muscle, were used to generate chimeric viruses. In situ hybridization analysis of different tissues from mice infected with the recombinant viruses, constructed by exchanging the 5′ non-coding region (5′NCR), structural and non-structural genes, demonstrated that the pancreo- and liver tropism map predominantly to CBV3 sequences within the capsid genes, evidently due to receptor recognition. Although the major neurotropism determinant in the CBV3 genome was in the capsid region, viruses containing the CAV9 capsid were also able to initiate infection in the central nervous system provided they contained the CBV3 5′NCR. The presence of the 5′NCR of CAV9 clearly enhanced muscle tissue tropism.

scholarly journals A GFP Reporter MR766-Based Flow Cytometry Neutralization Test for Rapid Detection of Zika Virus-Neutralizing Antibodies in Serum Specimens

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 66 ◽  
Author(s):  
Frumence ◽  
Viranaicken ◽  
Gadea ◽  
Desprès
Keyword(s):  
Flow Cytometry ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Health Concern ◽  
Structural Protein ◽  
Adult Mice ◽  
Gfp Reporter ◽  
Infected Cells ◽  
High Level

Zika virus (ZIKV) is an emerging arthropod-borne virus of major public health concern. ZIKV infection is responsible for congenital Zika disease and other neurological defects. Antibody-mediated virus neutralization is an essential component of protective antiviral immunity against ZIKV. In the present study, we assessed whether our GFP reporter ZIKV derived from African viral strain MR766 could be useful for the development of a flow cytometry neutralization test (FNT), as an alternative to the conventional plaque-reduction neutralization test (PRNT). To improve the efficacy of GFP-expressing MR766, we selected virus variant MR766GFP showing a high level of GFP signal in infected cells. A MR766GFP-based FNT was assayed with immune sera from adult mice that received ZIKBeHMR-2. The chimeric ZIKV clone ZIKBeHMR-2 comprises the structural protein region of epidemic strain BeH819015 into MR766 backbone. We reported that adult mice inoculated with ZIKBeHMR-2 developed high levels of neutralizing anti-ZIKV antibodies. Comparative analysis between MR766GFP-based FNT and conventional PRNT was performed using mouse anti-ZIKBeHMR-2 immune sera. Indistinguishable neutralization patterns were observed when compared with PRNT50 and FNT50. We consider that the newly developed MR766GFP-based FNT is a valid format for measuring ZIKV-neutralizing antibodies in serum specimens.

scholarly journals Emerging Novel GII.P16 Noroviruses Associated with Multiple Capsid Genotypes

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 535 ◽  
Author(s):  
Leslie Barclay ◽  
Jennifer L. Cannon ◽  
Mary E. Wikswo ◽  
Annie R. Phillips ◽  
Hannah Browne ◽  
...  
Keyword(s):  
Amino Acid ◽  
Severe Case ◽  
Molecular Data ◽  
Antigenic Drift ◽  
The Novel ◽  
Structural Protein ◽  
Protein Coding ◽  
Recombinant Viruses ◽  
The Us ◽  
Genomic Regions

Noroviruses evolve by antigenic drift and recombination, which occurs most frequently at the junction between the non-structural and structural protein coding genomic regions. In 2015, a novel GII.P16-GII.4 Sydney recombinant strain emerged, replacing the predominance of GII.Pe-GII.4 Sydney among US outbreaks. Distinct from GII.P16 polymerases detected since 2010, this novel GII.P16 was subsequently detected among GII.1, GII.2, GII.3, GII.10 and GII.12 viruses, prompting an investigation on the unique characteristics of these viruses. Norovirus positive samples (n = 1807) were dual-typed, of which a subset (n = 124) was sequenced to yield near-complete genomes. CaliciNet and National Outbreak Reporting System (NORS) records were matched to link outbreak characteristics and case outcomes to molecular data and GenBank was mined for contextualization. Recombination with the novel GII.P16 polymerase extended GII.4 Sydney predominance and increased the number of GII.2 outbreaks in the US. Introduction of the novel GII.P16 noroviruses occurred without unique amino acid changes in VP1, more severe case outcomes, or differences in affected population. However, unique changes were found among NS1/2, NS4 and VP2 proteins, which have immune antagonistic functions, and the RdRp. Multiple polymerase-capsid combinations were detected among GII viruses including 11 involving GII.P16. Molecular surveillance of protein sequences from norovirus genomes can inform the functional importance of amino acid changes in emerging recombinant viruses and aid in vaccine and antiviral formulation.

scholarly journals Insertion of cellular sequence and RNA recombination in the structural protein coding region of cytopathogenic bovine viral diarrhoea virus

2003 ◽  
Vol 84 (2) ◽  
pp. 447-452 ◽  
Author(s):  
Makoto Nagai ◽  
Yoshihiro Sakoda ◽  
Masashi Mori ◽  
Michiko Hayashi ◽  
Hiroshi Kida ◽  
...  
Keyword(s):  
Bovine Viral Diarrhoea Virus ◽  
Rna Recombination ◽  
Structural Protein ◽  
Bovine Viral Diarrhoea ◽  
Coding Region ◽  
Protein Coding ◽  
Diarrhoea Virus ◽  
Cellular Sequence

scholarly journals Evolutionary selection on synonymous codons in RNA G-quadruplex structural region

2021 ◽  
Author(s):  
Yuming Xu ◽  
Ting Qi ◽  
Zuhong Lu ◽  
Tong Zhou ◽  
Wanjun Gu
Keyword(s):  
Rna Structure ◽  
Nucleotide Composition ◽  
Sequence Information ◽  
Coding Region ◽  
Protein Coding ◽  
Translational Initiation ◽  
Evolutionary Selection ◽  
Synonymous Codons ◽  
G Quadruplex ◽  
Structural Region

ABSTRACTIn addition to the amino acid sequence information, synonymous codons can encode multiple regulatory and structural signals in protein coding region. In this study, we investigated how synonymous codons have been adapted to the formation of RNA G-quadruplex (rG4) structure. We found a universal selective pressure acting on synonymous codons to facilitate rG4 formation in five eukaryotic organisms. While G-rich codons are preferred in rG4 structural region, C-rich codons are selectively unpreferred for rG4 structures. Gene’s codon usage bias, nucleotide composition and evolutionary rate can account for the selective variations on synonymous codons among rG4 structures within a species. Moreover, rG4 structures in translational initiation region showed significantly higher selective pressures than those in translational elongation region. These results bring us another dimension of evolutionary selection on synonymous codons for proper RNA structure and function.

Selection on Rapidly Evolving Proteins in the Arabidopsis Genome

Genetics ◽  
2003 ◽  
Vol 163 (2) ◽  
pp. 723-733 ◽  
Author(s):  
Marianne Barrier ◽  
Carlos D Bustamante ◽  
Jiaye Yu ◽  
Michael D Purugganan
Keyword(s):  
Expressed Sequence Tag ◽  
Amino Acid Replacement ◽  
Adaptive Divergence ◽  
Coding Region ◽  
Protein Coding ◽  
Hierarchical Bayesian Analysis ◽  
Brassicaceae Species ◽  
Replacement Site ◽  
Orthologous Loci ◽  
Selection Intensities

Abstract Genes that have undergone positive or diversifying selection are likely to be associated with adaptive divergence between species. One indicator of adaptive selection at the molecular level is an excess of amino acid replacement fixed differences per replacement site relative to the number of synonymous fixed differences per synonymous site (ω = Ka/Ks). We used an evolutionary expressed sequence tag (EST) approach to estimate the distribution of ω among 304 orthologous loci between Arabidopsis thaliana and A. lyrata to identify genes potentially involved in the adaptive divergence between these two Brassicaceae species. We find that 14 of 304 genes (∼5%) have an estimated ω > 1 and are candidates for genes with increased selection intensities. Molecular population genetic analyses of 6 of these rapidly evolving protein loci indicate that, despite their high levels of between-species nonsynonymous divergence, these genes do not have elevated levels of intraspecific replacement polymorphisms compared to previously studied genes. A hierarchical Bayesian analysis of protein-coding region evolution within and between species also indicates that the selection intensities of these genes are elevated compared to previously studied A. thaliana nuclear loci.

scholarly journals Influence of the Leader protein coding region of foot-and-mouth disease virus on virus replication

2013 ◽  
Vol 94 (7) ◽  
pp. 1486-1495 ◽  
Author(s):  
Graham J. Belsham
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Initiation Codon ◽  
Coding Region ◽  
Protein Coding ◽  
Coding Sequence ◽  
Bhk Cells ◽  
Leader Protein ◽  
Mouth Disease Virus

The foot-and-mouth disease virus (FMDV) Leader (L) protein is produced in two forms, Lab and Lb, differing only at their amino-termini, due to the use of separate initiation codons, usually 84 nt apart. It has been shown previously, and confirmed here, that precise deletion of the Lab coding sequence is lethal for the virus, whereas loss of the Lb coding sequence results in a virus that is viable in BHK cells. In addition, it is now shown that deletion of the ‘spacer’ region between these two initiation codons can be tolerated. Growth of the virus precisely lacking just the Lb coding sequence resulted in a previously undetected accumulation of frameshift mutations within the ‘spacer’ region. These mutations block the inappropriate fusion of amino acid sequences to the amino-terminus of the capsid protein precursor. Modification, by site-directed mutagenesis, of the Lab initiation codon, in the context of the virus lacking the Lb coding region, was also tolerated by the virus within BHK cells. However, precise loss of the Lb coding sequence alone blocked FMDV replication in primary bovine thyroid cells. Thus, the requirement for the Leader protein coding sequences is highly dependent on the nature and extent of the residual Leader protein sequences and on the host cell system used. FMDVs precisely lacking Lb and with the Lab initiation codon modified may represent safer seed viruses for vaccine production.

Human DNA sequences homologous to a protein coding region conserved between homeotic genes of Drosophila

Cell ◽  
1984 ◽  
Vol 38 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Michael Levine ◽  
Gerald M. Rubin ◽  
Robert Tjian
Keyword(s):  
Dna Sequences ◽  
Homeotic Genes ◽  
Coding Region ◽  
Protein Coding ◽  
Human Dna
Sign in / Sign up

Export Citation Format

Share Document