Quasispecies as a matter of fact: Viruses and beyond

Ojosnegros, Samuel; Perales, Celia; Más, Antonio; Domingo, Esteban

doi:10.1016/j.virusres.2011.09.018

Cited by 67 publications

(59 citation statements)

References 195 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This assumes that there is limited withinhost diversity of the MRSA clone and that a single colony is sufficiently representative. However, as with viral infections, where a mixed population of a single lineage can be present within a host (Ojosnegros et al 2011), there is growing evidence that the same is true for bacteria. Harris et al (2013) sequenced 20 individual colonies of an MRSA clone isolated from the nose of a healthcare worker during a suspected outbreak, which demonstrated a cloud of genetic diversity.…”

Section: Discussionmentioning

confidence: 99%

Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting

et al. 2014

View full text Add to dashboard Cite

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial infection. Whole-genome sequencing of MRSA has been used to define phylogeny and transmission in well-resourced healthcare settings, yet the greatest burden of nosocomial infection occurs in resource-restricted settings where barriers to transmission are lower. Here, we study the flux and genetic diversity of MRSA on ward and individual patient levels in a hospital where transmission was common. We repeatedly screened all patients on two intensive care units for MRSA carriage over a 3-mo period. All MRSA belonged to multilocus sequence type 239 (ST 239). We defined the population structure and charted the spread of MRSA by sequencing 79 isolates from 46 patients and five members of staff, including the first MRSA-positive screen isolates and up to two repeat isolates where available. Phylogenetic analysis identified a flux of distinct ST 239 clades over time in each intensive care unit. In total, five main clades were identified, which varied in the carriage of plasmids encoding antiseptic and antimicrobial resistance determinants. Sequence data confirmed intra-and interwards transmission events and identified individual patients who were colonized by more than one clade. One patient on each unit was the source of numerous transmission events, and deep sampling of one of these cases demonstrated colonization with a ''cloud'' of related MRSA variants. The application of whole-genome sequencing and analysis provides novel insights into the transmission of MRSA in under-resourced healthcare settings and has relevance to wider global health.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting

et al. 2014

View full text Add to dashboard Cite

show abstract

“…This is at the higher end of the range of mutation rates for RNA viruses (11). However, as argued previously (9,12), measurements of mutation rates made under selective conditions and using variations of the fluctuation test provide only an approximate average value for a mixture of transitions and transversions, as often, mutations at various nucleotide residues can contribute to the selection of the resistant phenotype. Furthermore, the measurements are also affected by phenotypic masking of mutant genomes in wild-type envelopes and by the lower fitness of the MAR mutants than the parental population from which they were isolated (9,13).…”

mentioning

confidence: 84%

Determination of Spontaneous Mutation Frequencies in Measles Virus under Nonselective Conditions

Zhang

Rennick

Duprex

et al. 2013

J Virol

View full text Add to dashboard Cite

There is a paradox between the remarkable genetic stability of measles virus (MV) in the field and the high mutation rates implied by the frequency of the appearance of monoclonal antibody escape mutants generated when the virus is pressured to revert in vitro (S. J. Schrag, P. A. Rota, and W. J. Bellini, J. Virol. 73:51-54, 1999). We established a highly sensitive assay to determine frequencies of various categories of mutations in large populations of wild-type and laboratory-adapted MVs using recombinant viruses containing an additional transcription unit (ATU) encoding enhanced green fluorescent protein (EGFP). Single and double mutations were made in the fluorophore of EGFP to ablate fluorescence. The frequencies of reversion mutants in the population were determined by measuring the appearance of fluorescence indicating a revertant virus. This allows mutation rates to be measured under nonselective conditions, as phenotypic reversion to fluorescence requires only either a single-or a double-nucleotide change and amino acid substitution, which does not affect the length of the nonessential reporter protein expressed from the ATU. Mutation rates in MV are the same for wild-type and laboratory-adapted viruses, and they are an order of magnitude lower than the previous measurement assessed under selective conditions. The actual mutation rate for MV is approximately 1.8 ؋ 10؊6 per base per replication event.M easles is still a leading cause of vaccine-preventable death among children. The virus exhibits extremely high levels of infectivity, witnessed by its ability to infect the rare susceptible individuals present in highly vaccinated populations successfully (1). Measles virus (MV) is a single-stranded RNA virus with a genome of negative polarity, 15,894 nucleotides in length (2). It is a typical member of the subfamily Paramyxovirinae, with a genome that encodes six transcription units expressing six structural and at least two nonstructural proteins. The program of gene expression and the functions of the genes were well reviewed previously (3) and in essence do not differ from those of the wellstudied members of this group, such as Sendai virus and human parainfluenza virus 5 (hPIV5).The MV substitution rate has been much debated (4-7) because of the relative stability of MV in the field, but only a single paper has made an estimate of the spontaneous mutation rate in vitro (8). The high spontaneous mutation rates for RNA viruses result in the generation of a viral quasispecies consisting of a swarm of different viruses (9). This has important consequences for the properties of these viruses, especially in relation to evolutionary adaptability and their potential to make cross-species jumps (9). It is thus important to assess the mutation rate of these RNA viruses. Several methods have been employed to measure the mutation rates, but it has generally not been recognized that the determination of the actual mutation rates is impossible unless a number of parameters that are difficult to establish have been ...

show abstract

“…These studies use protein clustering not only to aid in organizing the 'unknown' sequences constituting the majority of many metaviromes, but offers a means to measure viral assemblage diversity (Hurwitz et al, 2012). Although this approach represents a significant advance forward, it is somewhat dependent on having assembled large contigs from metagenomic data sets and limited sequence variation within a virus population (Ojosnegros et al, 2011). In natural environments, viruses may not exist as a single genotype, but instead as a cloud of highly related genotypes.…”

Section: Introductionmentioning

confidence: 99%

Viral assemblage composition in Yellowstone acidic hot springs assessed by network analysis

et al. 2015

View full text Add to dashboard Cite

Understanding of viral assemblage structure in natural environments remains a daunting task. Total viral assemblage sequencing (for example, viral metagenomics) provides a tractable approach. However, even with the availability of next-generation sequencing technology it is usually only possible to obtain a fragmented view of viral assemblages in natural ecosystems. In this study, we applied a network-based approach in combination with viral metagenomics to investigate viral assemblage structure in the high temperature, acidic hot springs of Yellowstone National Park, USA. Our results show that this approach can identify distinct viral groups and provide insights into the viral assemblage structure. We identified 110 viral groups in the hot springs environment, with each viral group likely representing a viral family at the sub-family taxonomic level. Most of these viral groups are previously unknown DNA viruses likely infecting archaeal hosts. Overall, this study demonstrates the utility of combining viral assemblage sequencing approaches with network analysis to gain insights into viral assemblage structure in natural ecosystems.

show abstract

Quasispecies as a matter of fact: Viruses and beyond

Cited by 67 publications

References 195 publications

Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting

Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting

Determination of Spontaneous Mutation Frequencies in Measles Virus under Nonselective Conditions

Viral assemblage composition in Yellowstone acidic hot springs assessed by network analysis

Contact Info

Product

Resources

About