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At least 415 records · Page 23Linked to original sources
PubMed1985

[Possible commonality of origin of the RNA polymerase genes of plus-RNA-containing viruses of bacteria, plants and animals].

The data given testify that picornavirus RNA-dependent RNA-polymerase, RNA-polymerase encoded by the genome of MS2 phage and the certain polypeptides involved in the replication of RNA genomes of alphaviruses, tobamoviruses and tricornaviruses include the homologous stretches of the amino acids. The common sequences are located in the COOH-terminal regions of the viral proteins. These sequences have been found to be conserved also in RNA-replicase MS2 phage. The similarity of the primary structure between the RNA-polymerase phages and proteins of eucaryotic plus-RNA-containing viruses testifies in favour of the hypothesis on possible ancestral relationship of virus RNA-polymerases genes. These data point out that it is possible to localize an indispensable functional domain conserved upon evolutionary divergence of an ancestral RNA-polymerase gene. Such conservative region is recently found in the composition of RNA-dependent DNA-polymerases animals and plants virus. An attention is drawn to the region of protein similarity between conservative domains of viral RNA-dependent DNA-polymerases and RNA-polymerases.

Amino Acid Sequence↗
PubMed2005

Quasispecies made simple.

Quasispecies are clouds of genotypes that appear in a population at mutation-selection balance. This concept has recently attracted the attention of virologists, because many RNA viruses appear to generate high levels of genetic variation that may enhance the evolution of drug resistance and immune escape. The literature on these important evolutionary processes is, however, quite challenging. Here we use simple models to link mutation-selection balance theory to the most novel property of quasispecies: the error threshold-a mutation rate below which populations equilibrate in a traditional mutation-selection balance and above which the population experiences an error catastrophe, that is, the loss of the favored genotype through frequent deleterious mutations. These models show that a single fitness landscape may contain multiple, hierarchically organized error thresholds and that an error threshold is affected by the extent of back mutation and redundancy in the genotype-to-phenotype map. Importantly, an error threshold is distinct from an extinction threshold, which is the complete loss of the population through lethal mutations. Based on this framework, we argue that the lethal mutagenesis of a viral infection by mutation-inducing drugs is not a true error catastophe, but is an extinction catastrophe.

Genes, Lethal↗
PubMed1985

Evolutionary variants of Rous sarcoma virus: large deletion mutants do not result from homologous recombination.

Large deletion (LD) mutants of Prague strain Rous sarcoma virus, subgroup B (PrB), derived by serial undiluted passage through chicken (C/E) cells, were isolated and characterized. Individual LD viruses were initially isolated by cloning in soft agar of infected, chemically transformed quail (QT6) cells. Two regions of the PrB genome were deleted in the formation of the LD virus. This resulted in the junction of gag sequences in p12 to env sequences in gp37, and in the loss of the src gene. DNA restriction analysis of biologically active lambda Charon 27-LD recombinant clones indicated that individual LD viruses contained similar but not identical deletion endpoints. Two LD isolates, LD25 and LD85, were further subcloned into pBR322, and the deletion junctions were examined by DNA sequencing. Although the gag-env deletion endpoints were identical in the two subclones, heterogeneity was observed across the src deletion in that both mutants analyzed had the same 5' endpoint but slightly different 3' endpoints. In all cases, only a single homologous base (always an A residue) was found at the deletion endpoint. S1 nuclease analysis of the RNA from a number of QT6-LD clones gave similar results, indicating that the LD population was composed of viruses with similar but not identical deletion endpoints. Such viruses may have been generated from errors during reverse transcription of the virion RNA with subsequent selection assuring their dominance in the population.

Avian Sarcoma Viruses↗
PubMed1997

Forced evolution of a regulatory RNA helix in the HIV-1 genome.

The 5'and 3'end of the HIV-1 RNA genome forms a repeat (R) element that encodes a double stem-loop structure (the TAR and polyA hairpins). Phylogenetic analysis of the polyA hairpin in different human and simian immunodeficiency viruses suggests that the thermodynamic stability of the helix is fine-tuned. We demonstrated previously that mutant HIV-1 genomes with a stabilized or destabilized hairpin are severely replication-impaired. In this study, we found that the mutant with a destabilized polyA hairpin structure is conditionally defective. Whereas reduced replication is measured in infections at the regular temperature (37 degrees C), this mutant is more fit than the wild-type virus at reduced temperature (33 degrees C). This observation of a temperature-dependent replication defect underscores that the stability of this RNA structure is critical for function. An extensive analysis of revertant viruses was performed to further improve the understanding of the critical sequence and structural features of the element under scrutiny. The virus mutants with a stabilized or destabilized hairpin were used as a starting point in multiple, independent selections for revertant viruses with compensatory mutations. Both mutants reverted to hairpins with wild-type stability along various pathways by acquisition of compensatory mutations. We identified 19 different revertant HIV-1 forms with improved replication characteristics, providing a first look at some of the peaks in the total sequence landscape that are compatible with virus replication. These experiments also highlight some general principles of RNA structure building.

Base Sequence↗
PubMed1999

Multiple mitochondrial viruses in an isolate of the Dutch Elm disease fungus Ophiostoma novo-ulmi.

The nucleotide sequences of three mitochondrial virus double-stranded (ds) RNAs, RNA-4 (2599 nucleotides), RNA-5 (2474 nucleotides), and RNA-6 (2343 nucleotides), in a diseased isolate Log1/3-8d2 (Ld) of the Dutch elm disease fungus Ophiostoma novo-ulmi have been determined. All these RNAs are A-U-rich (71-73% A + U residues). Using the fungal mitochondrial genetic code in which UGA codes for tryptophan, the positive-strand of each of RNAs 4, 5, and 6 contains a single open reading frame (ORF) with the potential to encode a protein of 783, 729, and 695 amino acids, respectively, all of which contain conserved motifs characteristic of RNA-dependent RNA polymerases (RdRps). Sequence comparisons showed that these RNAs are related to each other and to a previously characterized RNA, RNA-3a, from the same O. novo-ulmi isolate, especially within the RdRp-like motifs. However, the overall RNA nucleotide and RdRp amino acid sequence identities were relatively low (43-55% and 20-32%, respectively). The 5'- and 3'-terminal sequences of these RNAs are different, but they can all be folded into potentially stable stem-loop structures. Those of RNA-4 and RNA-6 have inverted complementarity, potentially forming panhandle structures. Their molecular and biological properties indicate that RNAs 3a, 4, 5, and 6 are the genomes of four different viruses, which replicate independently in the same cell. These four viruses are also related to a mitochondrial RNA virus from another fungus, Cryphonectria parasitica, recently designated the type species of the Mitovirus genus of the Narnaviridae family, and to a virus from the fungus Rhizoctonia solani. It is proposed that the four O. novo-ulmi mitochondrial viruses are assigned to the Mitovirus genus and designated O. novo-ulmi mitovirus (OnuMV) 3a-Ld, 4-Ld, 5-Ld, and 6-Ld, respectively. Northern blot analysis indicated that O. novo-ulmi Ld nucleic acid extracts contain more single-stranded (ss, positive-stranded) RNA than dsRNA for all three newly described mitoviruses. O. novo-ulmi RNA-7, previously believed to be a satellite-like RNA, is shown to be a defective RNA, derived from OnuMV4-Ld RNA by multiple internal deletions. OnuMV4-Ld is therefore the helper virus for the replication of both RNA-7 and another defective RNA, RNA-10. Sequence comparisons indicate that RNA-10 could be derived from RNA-7, as previously suggested, or derived directly from RNA-4.

3' Untranslated Regions↗
PubMed2000

Testing the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus.

A Monte Carlo method was used to test the extent of sequence similarity among viroids, satellite RNAs, and hepatitis delta virus. This analysis revealed that there is insufficient sequence similarity among these pathogens to support the hypothesis that they have a common evolutionary origin. Furthermore, while definite patterns of sequence similarity were observed among some viroids, there was a clear lack of overall similarity, indicating that a monophyletic origin for even this group cannot be reliably supported from sequence data alone.

Biological Evolution↗
PubMed2001

Molecular epidemiology of dengue type 2 virus in Venezuela: evidence for in situ virus evolution and recombination.

Epidemic outbreaks of dengue fever (DF) were first recorded in Venezuela in 1978 and were followed by the emergence of dengue haemorrhagic fever (DHF) outbreaks in 1989. To gain a better understanding of the nature of these epidemics, the complete envelope (E) gene sequence of 34 Venezuelan dengue type 2 (DEN-2) viruses, isolated between 1997 and 2000 was determined. Of these isolates, 16 were from patients with DF and 17 were from patients diagnosed with DHF. There were no diagnostic sequence differences between them, suggesting that the E gene alone does not determine disease severity. These sequence data were also used in phylogenetic comparisons with a global sample of DEN-2 viruses, including strains collected previously from Venezuela. This analysis revealed that the ancestors of the Venezuelan viruses were Asian in origin, implying that a DEN-2 virus strain from this region was introduced into Venezuela and the wider Caribbean region during the late 1970s or the early 1980s. The phylogenetic trees further indicate that evolution of DEN-2 virus in Venezuela has occurred in situ, with differentiation into a number of distinct but co-circulating lineages, rather than the repeated introduction of new strains from other localities. By incorporating additional sequence data from the virus capsid, premembrane and membrane genes, evidence is provided that a single Venezuelan strain sequenced previously, designated Mara4, is a recombinant virus, incorporating genome sequence from Venezuelan and Asian parental viruses.

Asia↗
PubMed2003

Fitness distributions in exponentially growing asexual populations.

We explore a mean-field model for the evolution of exponentially growing populations of mutating replicators. Motivated by recent in vitro experiments devised to analyze phenotypic properties of bacterial and viral populations subjected to serial population transfers, we allow our in silico individuals to undergo unrestricted growth before applying bottleneck events. Different dynamical regimes of our model can be mapped to different experimental situations. Numerical and analytical results for fitness distributions calculated at the statistically stationary states of the dynamics compare favorably with available experimental data. Our model and results provide a common framework to better understand populations evolving under different selection pressures.

Biological Evolution↗
PubMed2006

Unbiased in vitro selection reveals the unique character of the self-cleaving antigenomic HDV RNA sequence.

In order to revisit the architecture of the catalytic center of the antigenomic hepatitis delta virus (HDV) ribozyme we developed an unbiased in vitro selection procedure that efficiently selected novel variants from a relatively small set of sequences. Using this procedure we examined all possible variants from a pool of HDV ribozymes that had been randomized at 25 positions (4(25)). The isolated set of sequences shows more variability than do the natural variants. Nucleotide variations were found at all randomized positions, even at positions when the general belief was that the specific base was absolutely required for catalytic activity. Covariation analysis supports the presence of several base pairs, although it failed to propose any new tertiary contacts. HDV ribozyme appears to possess a greater number of constraints, in terms of sequences capable of supporting the catalysed cleavage, than do other catalytic RNAs. This supports the idea that the appearance of this catalytic RNA structure has a low probability (i.e. is a rare event), which may explain why to date it has been found in nature only in the HDV. These contrasts with the hammerhead self-cleaving motif that is proposed to have multiple origins, and that is widespread among different organisms. Thus, just because a self-cleaving RNA motif is small does not imply that it occurs easily.

Catalytic Domain↗
PubMed2025

Molecular Evolution and Zoonotic Potential of Muju Virus (Orthohantavirus puumalaense) in Craseomys regulus, Republic of Korea.

Orthohantavirus puumalaense causes hemorrhagic fever with renal syndrome in Europe, with Puumala virus (PUUV) as its primary representative. Muju virus (MUJV), harbored by Craseomys regulus, an Arvicolinae rodent species endemic to the Republic of Korea (ROK), is also a genotype of O. puumalaense. However, their genomic diversity and zoonotic potential remain largely unknown. To investigate their prevalence, 185 voles were collected from 23 regions of the ROK between 2012 and 2023. Serological assays detected anti-PUUV immunoglobulin G antibodies in five samples (3.1%), whereas reverse-transcription polymerase chain reaction confirmed MUJV RNA in identical specimens (2.7%). Amplicon-based nanopore sequencing facilitates near-complete genome recovery, enabling high-resolution comparative analysis. Phylogenetic analysis revealed distinct genetic lineages in Gangwon and Jeollabuk Provinces. Evolutionary rate estimates indicated greater sequence divergence in the S and L segments than in the M segment. A zoonotic risk assessment revealed that most MUJV variants exhibited moderate-to-high spillover potential. The molecular detection of MUJV in Cheorwon, Gangwon Province, expands its known geographic range and provides the first molecular evidence of MUJV circulation in this region. These findings highlight the need for continued surveillance and seroprevalence studies of MUJV to assess its potential for human exposure and public health relevance in the ROK.

Animals↗