Project description:Citrus tristeza virus (CTV), a member of the aphid-transmitted closterovirus group, is the causal agent of the notorious tristeza disease in several citrus species worldwide. The codon usage patterns of viruses reflect the evolutionary changes for optimization of their survival and adaptation in their fitness to the external environment and the hosts. The codon usage adaptation of CTV to specific citrus hosts remains to be studied; thus, its role in CTV evolution is not clearly comprehended. Therefore, to better explain the host?virus interaction and evolutionary history of CTV, the codon usage patterns of the coat protein (CP) genes of 122 CTV isolates originating from three economically important citrus hosts (55 isolate from Citrus sinensis, 38 from C. reticulata, and 29 from C. aurantifolia) were studied using several codon usage indices and multivariate statistical methods. The present study shows that CTV displays low codon usage bias (CUB) and higher genomic stability. Neutrality plot and relative synonymous codon usage analyses revealed that the overall influence of natural selection was more profound than that of mutation pressure in shaping the CUB of CTV. The contribution of high-frequency codon analysis and codon adaptation index value show that CTV has host-specific codon usage patterns, resulting in higheradaptability of CTV isolates originating from C. reticulata (Cr-CTV), and low adaptability in the isolates originating from C. aurantifolia (Ca-CTV) and C. sinensis (Cs-CTV). The combination of codon analysis of CTV with citrus genealogy suggests that CTV evolved in C. reticulata or other Citrus progenitors. The outcome of the study enhances the understanding of the factors involved in viral adaptation, evolution, and fitness toward their hosts. This information will definitely help devise better management strategies of CTV.
Project description:Background:Flaviviridae viruses are single-stranded, positive-sense RNA viruses, which threat human constantly mediated by mosquitoes, ticks, and sandflies. Considering the recent increase in the prevalence of the family virus and its risk potential, we investigated the codon usage pattern to understand its evolutionary processes and provide some useful data to develop the medications for most of Flaviviridae viruses. Results:The overall extent of codon usage bias in 65 Flaviviridae viruses is low with the average value of GC contents being 50.5% and the highest value being 55.9%; the lowest value is 40.2%. ENC values of Flaviviridae virus genes vary from 48.75 to 57.83 with a mean value of 55.56. U- and A-ended codons are preferred in the Flaviviridae virus. Correlation analysis shows that the positive correlation between ENC value and GC content at the third nucleotide positions was significant in this family virus. The result of analysis of ENC, neutrality plot analysis, and correlation analysis revealed that codon usage bias of all the viruses was affected mainly by natural selection. Meanwhile, according to correspondence analysis (CoA) based on RSCU and phylogenetic analysis, the Flaviviridae viruses mainly are made up of two groups, Group I (Yellow fever virus, Apoi virus, Tembusu virus, Dengue virus 1, and others) and Group II (West Nile virus lineage 2, Japanese encephalitis virus, Usutu virus, Kedougou virus, and others). Conclusions:All in, the bias of codon usage pattern is affected not only by compositional constraints but also by natural selection. Phylogenetic analysis also illustrates that codon usage bias of virus can serve as an effective means of evolutionary classification in Flaviviridae virus.
Project description:Bluetongue virus (BTV) is a double-stranded RNA virus with multiple segments and belongs to the genus Orbivirus within the family Reoviridae. BTV is spread to livestock through its dominant vector, biting midges of genus Culicoides. Although great progress has been made in genomic analyses, it is not fully understood how BTVs adapt to their hosts and evade the host's immune systems. In this study, we retrieved BTV genome sequences from the National Center for Biotechnology Information (NCBI) database and performed a comprehensive research to explore the codon usage patterns in 50 BTV strains. We used bioinformatic approaches to calculate the relative synonymous codon usage (RSCU), codon adaptation index (CAI), effective number of codons (ENC), and other indices. The results indicated that most of the overpreferred codons had A-endings, which revealed that mutational pressure was the major force shaping codon usage patterns in BTV. However, the influence of natural selection and geographical factors cannot be ignored on viral codon usage bias. Based on the RSCU values, we performed a comparative analysis between BTVs and their hosts, suggesting that BTVs were inclined to evolve their codon usage patterns that were comparable to those of their hosts. Such findings will be conducive to understanding the elements that contribute to viral evolution and adaptation to hosts.
Project description:Background and aimClassical swine fever (CSF), caused by CSF virus (CSFV), is a highly contagious disease in pigs causing 100% mortality in susceptible adult pigs and piglets. High mortality rate in pigs causes huge economic loss to pig farmers. CSFV has a positive-sense RNA genome of 12.3 kb in length flanked by untranslated regions at 5' and 3' end. The genome codes for a large polyprotein of 3900 amino acids coding for 11 viral proteins. The 1300 codons in the polyprotein are coded by different combinations of three nucleotides which help the infectious agent to evolve itself and adapt to the host environment. This study performed and employed various methods/techniques to estimate the changes occurring in the process of CSFV evolution by analyzing the codon usage pattern.Materials and methodsThe evolution of viruses is widely studied by analyzing their nucleotides and coding regions/codons using various methods. A total of 115 complete coding regions of CSFVs including one complete genome from our laboratory (MH734359) were included in this study and analysis was carried out using various methods in estimating codon usage bias and evolution. This study elaborates on the factors that influence the codon usage pattern.ResultsThe effective number of codons (ENC) and relative synonymous codon usage showed the presence of codon usage bias. The mononucleotide (A) has a higher frequency compared to the other mononucleotides (G, C, and T). The dinucleotides CG and CC are underrepresented and overrepresented. The codons CGT was underrepresented and AGG was overrepresented. The codon adaptation index value of 0.71 was obtained indicating that there is a similarity in the codon usage bias. The principal component analysis, ENC-plot, Neutrality plot, and Parity Rule 2 plot produced in this article indicate that the CSFV is influenced by the codon usage bias. The mutational pressure and natural selection are the important factors that influence the codon usage bias.ConclusionThe study provides useful information on the codon usage analysis of CSFV and may be utilized to understand the host adaptation to virus environment and its evolution. Further, such findings help in new gene discovery, design of primers/probes, design of transgenes, determination of the origin of species, prediction of gene expression level, and gene function of CSFV. To the best of our knowledge, this is the first study on codon usage bias involving such a large number of complete CSFVs including one sequence of CSFV from India.
Project description:Eighteen of the 20 amino acids are each encoded by more than one synonymous codon. Due to differential transfer RNA supply within the cell, synonymous codons are not used with equal frequency, a phenomenon termed codon usage bias (CUB). Previous studies have demonstrated that CUB of endogenous genes trans-regulates the translational efficiency of other genes. We hypothesized similar effects for CUB of exogenous genes on host translation, and tested it in the case of viral infection, a common form of naturally occurring exogenous gene translation. We analysed public Ribo-Seq datasets from virus-infected yeast and human cells and showed that virus CUB trans-regulated tRNA availability, and therefore the relative decoding time of codons. Manipulative experiments in yeast using 37 synonymous fluorescent proteins confirmed that an exogenous gene with CUB more similar to that of the host would apply decreased translational load on the host per unit of expression, whereas expression of the exogenous gene was elevated. The combination of these two effects was that exogenous genes with CUB overly similar to that of the host severely impeded host translation. Finally, using a manually curated list of viruses and natural and symptomatic hosts, we found that virus CUB tended to be more similar to that of symptomatic hosts than that of natural hosts, supporting a general deleterious effect of excessive CUB similarity between virus and host. Our work revealed repulsion between virus and host CUBs when they are overly similar, a previously unrecognized complexity in the coevolution of virus and host.
Project description:Viruses show noticeable evolution to adapt and reproduce within their hosts. Theoretically, patterns and factors that affect the codon usage of viruses should reflect evolutionary changes that allow them to optimize their codon usage to their hosts. Some software tools can analyze the codon usage of organisms; however, their performance has room for improvement, as these tools do not focus on examining the codon usage co-adaptation between viruses and their hosts. This paper describes the vhcub R package, which is a crucial tool used to analyze the co-adaptation of codon usage between a virus and its host, with several implementations of indices and plots. The tool is available from: https://cran.r-project.org/web/packages/vhcub/.
Project description:Viral codon usage bias may be the product of a number of synergistic or antagonistic factors, including genomic nucleotide composition, translational selection, genomic architecture, and mutational or repair biases. Most studies of viral codon bias evaluate only the relative importance of genomic base composition and translational selection, ignoring other possible factors. We analyzed the codon preferences of ssRNA (luteoviruses and potyviruses) and ssDNA (geminiviruses) plant viruses that infect translationally distinct monocot and dicot hosts. We found that neither genomic base composition nor translational selection satisfactorily explains their codon usage biases. Furthermore, we observed a strong relationship between the codon preferences of viruses in the same family or genus, regardless of host or genomic nucleotide content. Our results suggest that analyzing codon bias as either due to base composition or translational selection is a false dichotomy that obscures the role of other factors. Constraints such as genomic architecture and secondary structure can and do influence codon usage in plant viruses, and likely in viruses of other hosts.
Project description:Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
Project description:Lumpy skin disease virus (LSDV) causes lumpy skin disease (LSD) in livestock, which is a double-stranded DNA virus that belongs to the genus Capripoxvirus of the family Poxviridae. LSDV is an important poxvirus that has spread out far and wide to become distributed worldwide. It poses serious health risks to the host and causes considerable negative socioeconomic impact on farmers financially and on cattle by causing ruminant-related diseases. Previous studies explained the population structure of the LSDV within the evolutionary time scale and adaptive evolution. However, it is still unknown and remains enigmatic as to how synonymous codons are used by the LSDV. Here, we used 53 LSDV strains and applied the codon usage bias (CUB) analysis to them. Both the base content and the relative synonymous codon usage (RSCU) analysis revealed that the AT-ended codons were more frequently used in the genome of LSDV. Further low codon usage bias was calculated from the effective number of codons (ENC) value. The neutrality plot analysis suggested that the dominant factor of natural selection played a role in the structuring of CUB in LSDV. Additionally, the results from a comparative analysis suggested that the LSDV has adapted host-specific codon usage patterns to sustain successful replication and transmission chains within hosts (Bos taurus and Homo sapiens). Both natural selection and mutational pressure have an impact on the codon usage patterns of the protein-coding genes in LSDV. This study is important because it has characterized the codon usage pattern in the LSDV genomes and has provided the necessary data for a basic evolutionary study on them.