The nucleoprotein (NP) of influenza A virus (IAV) is associated with many different functions including host range restriction. Multiple sequence alignment analyses of 748 NP gene sequences from GenBank revealed a highly conserved region of 60 nucleotides within the ORF at the 3'-ends of the cRNA, in some codons even silent mutations were not found. This suggests that the RNA structure integrity within this region is crucial for IAV replication. To explore the impact of these conserved nucleotides for viral replication we created mutant viruses with one or more silent mutations in the respective region of the NP gene of the IAV strain A/WSN/33 (H1N1) (WSN). Assessment of viral replication of these WSN mutant viruses showed significant growth disadvantages when compared to the corresponding parental strain. On the basis of these findings we tested whether the attenuation of IAV by introduction of silent mutations into the NP gene may serve as a strategy to create a live attenuated vaccine. Mice vaccinated with the attenuated WSN mutant survived a lethal challenge dose of wild type WSN virus or the mouse adapted pandemic H1N1v strain A/Hamburg/4/2009. Thus, introduction of silent mutations in the NP of IAV is a feasible approach for a novel vaccination strategy allowing attenuation of the master strain but leaves the antigenicity of the gene product unaltered. This principle is potentially applicable for all viruses with segmented genomes.
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http://dx.doi.org/10.1016/j.vaccine.2012.04.070 | DOI Listing |
HLA
January 2025
Kirov Hematology and Blood Transfusion Research Institute Under the Federal Medicine and Biology Agency, Federal State Budget Research Institution, Kirov, Russia.
Four novel HLA-B noncoding variants detected by next-generation sequencing: HLA-B*07:02:107, -B*08:01:78, -B*15:01:89 and -B*52:01:58.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
SynVaccine Ltd, Ramat Hachayal, 3 Golda Meir Street, Science Park, Nes Ziona 7403648, Israel.
Many viruses of the Flaviviridae family, including the Zika virus (ZIKV), are human pathogens of significant public health concerns. Despite extensive research, there are currently no approved vaccines available for ZIKV and specifically no live-attenuated Zika vaccine. In this current study, we suggest a novel computational algorithm for generating live-attenuated vaccines via the introduction of silent mutation into regions that undergo selection for strong or weak local RNA folding or into regions that exhibit medium levels of sequence conservation.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Endocrinology, The Second Affiliated Hospital of Fujian Medical University, No. 950 Donghai Street, Fengze District, Quanzhou, 362000, Fujian, China.
The significance of ALKBH5 in erasing mRNA methylation in mRNA biogenesis, decay, and translation control has emerged as a prominent research focus. Additionally, ALKBH5 is associated with the development of numerous human cancers. However, it remains unclear whether ALKBH5 regulates the growth and metastasis of papillary thyroid carcinoma (PTC).
View Article and Find Full Text PDFZhonghua Yi Xue Yi Chuan Xue Za Zhi
January 2025
Precision Medical Lab Center, People's Hospital of Yangjiang, Yangjiang, Guangdong 529500, China.
Objective: To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.
Methods: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd.
bioRxiv
December 2024
Department of Biochemistry and Molecular Genetics, University of Colorado, Denver - Anschutz Medical Campus.
Organisms with smaller genomes often perform multiple functions using one multi-subunit protein complex. The Silent Information Regulator complex (SIRc) carries out all of the core functions of heterochromatin. SIR complexes first drive the initiation and spreading of histone deacetylation in an iterative manner.
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