MicroRNAs (miRNAs) are small, noncoding RNA molecules that play important roles in the regulation of gene expression of the cell. Recent studies have described cytoplasmic RNA virus genome- derived miRNAs. Moreover, miRNAs have also been encountered in the reverse strand of the viral mRNA, revealing the presence of miRNAs in replication intermediaries. In order to get insight into the possible role of Hepatitis C Virus (HCV) antigenome in relation to miRNA coding, we computationally identified potential miRNAs on the antigenome of HCV reference strain H77. By utilizing a series of bioinformatics tools, we identified a miRNA present in the antigenomeof HCV H77 strain. This miRNA maps in the 5’non-translated region (5’UTR) of the HCV genome and is found to be conserved among HCV genotypes and sub-types. In silico target prediction generated 17 cellular genes. These potential targets are involved in apoptosis as well as immune response pathways, suggesting that they could play a role in the pathogenesis caused by viral infection. The results of these studies revealed the presence of a viral miRNA in the negative-sense RNA strand used as a replication template for the HCV genome, as observed for other RNA viruses.

10.4236/ns.2016.84021

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Phylogenetic Analysis of Coxsackie B Viruses Reveals Genomic Plasticity and Adaptation as Studied by Codon Usage Patterns

Journal of Medical Microbiology & Diagnosis (2014)

Ricardo Recarey Gonzalo Moratorio

Coxsackie B viruses (CVB) are associated with serious illnesses in humans. In this study, the patterns of synonymous codon usage in CVB have been studied through multivariate statistical methods. Effective number of codons (ENC) indicates that the overall extent of codon usage bias in CVB is not significant. The relative dinucleotide abundances suggest that codon usage bias in CVB genomes is influenced by underlying biases of dinucleotide frequencies. The distribution of CVB ORFs along the plane defined by the first two axes of correspondence analysis (COA) showed that different genotypes, as well as strains known to infect different cell types, are located at different places in the plane suggesting that CVB codon usage is reflecting an evolutionary process. The results of these studies suggest that CVB genomic biases are the result of co-evolution of translation adaptation to different cell environments and probably the need to escape anti-viral cell defenses.

10.4172/2161-0703.s4-001

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Bayesian Coalescent Analysis of the Intra-Host Evolution of Hepatitis C Virus: Memory Genomes and Clinical Implications

Natural Science (2014)

Ricardo Recarey Juan Cristina

Genetic variability plays a key role in the biology and medical treatment of RNA viruses. As an RNA virus, Hepatitis C virus (HCV) replicate as complex distributions of closely related genomes termed viral quasispecies. The behavior of the evolving HCV quasispecies population is influenced by the ensemble of mutants that compose the viral population. One such influence is the presence of minority subpopulations, termed memory genomes, in the mutant spectra. Biologically relevant mutants have been previously observed to be present as memory genomes in RNA viral populations. For that reason, an in-depth analysis of HCV quasispecies populations is crucial for our understanding viral evolution, drug resistance and therapy outcome. Recently developed next-generation sequencing (NGS) platforms make it possible to investigate viral quasispecies at much greater detail. In order to gain insight into these matters, we have performed a Bayesian coalescent analysis of hypervariable region 1 (HVR1) sequences of a HCV quasispecies population circulating in a chronic patient, recently obtained by ultra-deep sequencing. The results of these studies revealed a mean rate of evolution of HCV HVR1 of the intra-host quasispecies population of 4.80 × 10-2 amino acid substitutions/site/year. A sharp and rapid diversification of the HCV quasispecies isolated from the patient in three different sub-populations was observed. The most abundant sequence in the quasispecies population was not found to be the center of a tight and complex network around this sequence, suggesting that the quasispecies population as a whole efficiently explore a wide sequence space. Co-evolution of relevant amino acid sites had been identified in the HVR1. This speaks of the possible roll of these residues in HVR1 to allow the virus to shift between combinations of residues to escape the immune system while retaining its structure and functions. The results of these studies highlight the importance of minority genomes in HCV population history and evolution, the mutant clouds as reservoirs of phenotypic and genetic variants for virus adaptability, as well as the roll of the mutant spectra to overcome selective constraints.

Viral quasispecies

Coalescent theory

Viral evolution

Hypervariable region

10.4236/ns.2014.69061

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Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region

Virology Journal (2007)

Gonzalo Moratorio Mariela Martínez María Fernanda Gutiérrez Katiuska González Rodney Colina

Abstract Background Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR) sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America. Methods Phylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program. Results Phylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region. Conclusion Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population. The coexistence of distinct type 1 HCV subpopulations is consistent with quasispecies dynamics, and suggests that multiple coexisting subpopulations may allow the virus to adapt to its human host populations.

Lineage (genetic)

Coding region

Viral quasispecies

10.1186/1743-422x-4-79

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