ORCID Profile
0000-0002-8797-2667
Current Organisations
Royal Veterinary College
,
University of Oxford
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Publisher: American Society for Microbiology
Date: 15-10-2012
DOI: 10.1128/JVI.00701-12
Abstract: Feline calicivirus (FCV) is an important pathogen of domestic cats and a frequently used model of human caliciviruses. Here we use an epidemiologically rigorous s ling framework to describe for the first time the phylodynamics of a calicivirus at regional and national scales. A large number of FCV strains cocirculated in the United Kingdom at the national and community levels, with no strain comprising more than 5% and 14% of these populations, respectively. The majority of strains exhibited a relatively restricted geographical range, with only two strains (one field virus and one vaccine virus) spreading further than 100 km. None of the field strains were identified outside the United Kingdom. Temporally, while some strains persisted locally for the majority of the study, others may have become locally extinct. Evolutionary analysis revealed a radial phylogeny with little bootstrap support for nodes above the strain level. In most cases, spatially and temporally erse strains intermingled in the phylogeny. Together, these data suggest that current FCV evolution is not associated with selective competition among strains. Rather, the genetic and antigenic landscape in each geographical location is highly complex, with many strains cocirculating. These variants likely exist at the community level by a combination of de novo evolution and occasional gene flow from the wider national population. This complexity provides a benchmark, for the first time, against which vaccine cross-protection at both local and national levels can be judged.
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S1567-1348(02)00153-3
Abstract: Among the members of the genus Flavivirus are several important human pathogens, including the dengue (DEN) and Japanese encephalitis (JE) viruses. From the analysis of gene sequence data of s les of these virus populations it is possible to infer phylogenetic relationships, which in turn can yield important epidemiological information, including their demographic history in humans. In this study, we use a recently developed method, based on coalescent theory, to infer the population dynamics of a variety of mosquito-borne flaviviruses. Our study involves the testing of alternative hypotheses, the estimation of confidence intervals around demographic model parameter values, and the placing of the maximum likelihood (ML) demographic model into a "real time" epidemiological history. We reveal that all the Flavivirus populations studied are growing at an exponential rate, with the rates of population growth of dengue virus serotypes 2 and 3 increasing rapidly in the recent past, and that of Japanese encephalitis virus changing from constant population size to exponential growth within the last century. We therefore demonstrate that the use of these coalescent methods may be extremely valuable in monitoring responses to interventions such as vaccination or vector control.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.MEEGID.2013.03.015
Abstract: Recombination plays an important role in shaping the genetic ersity of a number of DNA and RNA viruses. Although some recent studies have reported bioinformatic evidence of mosaic sequences in a variety of influenza A viruses, it remains controversial as to whether these represent bona fide natural recombination events or laboratory artifacts. Importantly, mosaic genome structures can create significant topological incongruence during phylogenetic analyses, which can mislead additional phylogeny-based molecular evolutionary analyses such as molecular clock dating, the detection of selection pressures and phylogeographic inference. As a result, there is a strong need for systematic screenings for mosaic structures within the influenza virus genome database. We used a combination of sequence-based and phylogeny-based methods to identify 388 mosaic influenza genomic segments, of which 332 are previously unreported and are significantly supported by phylogenetic methods. It is impossible, however, to ascertain whether these represent natural recombinants. To facilitate the future identification of recombinants, reference sets of non-recombinant sequences were selected for use in an automatic screening protocol for detecting mosaic sequences. Tests using real and simulated mosaic sequences indicate that our screening protocol is both sensitive (average >90%) and accurate (average >77%) enough to identify a range of different mosaic patterns. The relatively high prevalence of mosaic influenza virus sequences implies that efficient systematic screens, such as that proposed here, should be performed routinely to detect natural recombinant strains, potential laboratory artifacts, and sequencing contaminants either prior to sequences being deposited in GenBank or before they are used for phylogenetic analyses.
Publisher: American Society for Microbiology
Date: 15-11-2009
DOI: 10.1128/JVI.00884-09
Abstract: Hepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed. We performed full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a infection and assessed genomic viral variability in comparison to other HCV subtypes. Two novel regions of intragenotypic hypervariability within the envelope protein E2, of HCV genotype 3a, were identified. We named these regions HVR495 and HVR575. They consisted of flanking conserved hydrophobic amino acids and central variable residues. A 5-amino-acid insertion found only in genotype 3a and a putative glycosylation site is contained within HVR575. Evolutionary analysis of E2 showed that positively selected sites within genotype 3a infection were largely restricted to HVR1, HVR495, and HVR575. Further analysis of clonal viral populations within single hosts showed that viral variation within HVR495 and HVR575 were subject to intrahost positive selecting forces. Longitudinal analysis of four patients with acute HCV subtype 3a infection s led at multiple time points showed that positively selected mutations within HVR495 and HVR575 arose early during primary infection. HVR495 and HVR575 were not present in HCV subtypes 1a, 1b, 2a, or 6a. Some variability that was not subject to positive selection was present in subtype 4a HVR575. Further defining the functional significance of these regions may have important implications for genotype 3a E2 virus-receptor interactions and for vaccine studies that aim to induce cross-reactive anti-E2 antibodies.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-04-2021
Abstract: For two-dose vaccines against severe acute respiratory syndrome coronavirus 2, some jurisdictions have decided to delay the second dose to rapidly get the vaccine into more people. The consequences of deviating from manufacturer-prescribed dosing regimens are unknown but will depend on the strength of immune responses to the vaccines. Saad-Roy et al. took a modeling approach to tackling the inevitable uncertainties facing vaccine rollout. The authors found that although one-dose strategies generally reduce infections in the short term, in the long term, the outcome depends on immune robustness. A one-dose strategy may increase the potential for antigenic evolution if immune responses are suboptimal and the virus continues to replicate in some vaccinated people, potentially leading to immune-escape mutations. It is critical to gather serological data from vaccinated people and, to avoid negative outcomes, to r up vaccination efforts worldwide. Science , this issue p. 363
Publisher: Elsevier BV
Date: 03-2017
Publisher: American Society for Microbiology
Date: 15-12-2005
DOI: 10.1128/JVI.79.23.14680-14687.2005
Abstract: Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic fever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic ersity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral ersity between outbreaks.
Publisher: Springer Science and Business Media LLC
Date: 06-2009
DOI: 10.1038/NATURE08182
Abstract: In March and early April 2009, a new swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the United States. During the first few weeks of surveillance, the virus spread worldwide to 30 countries (as of May 11) by human-to-human transmission, causing the World Health Organization to raise its pandemic alert to level 5 of 6. This virus has the potential to develop into the first influenza pandemic of the twenty-first century. Here we use evolutionary analysis to estimate the timescale of the origins and the early development of the S-OIV epidemic. We show that it was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak. A phylogenetic estimate of the gaps in genetic surveillance indicates a long period of uns led ancestry before the S-OIV outbreak, suggesting that the reassortment of swine lineages may have occurred years before emergence in humans, and that the multiple genetic ancestry of S-OIV is not indicative of an artificial origin. Furthermore, the uns led history of the epidemic means that the nature and location of the genetically closest swine viruses reveal little about the immediate origin of the epidemic, despite the fact that we included a panel of closely related and previously unpublished swine influenza isolates. Our results highlight the need for systematic surveillance of influenza in swine, and provide evidence that the mixing of new genetic elements in swine can result in the emergence of viruses with pandemic potential in humans.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 16-01-2004
Abstract: A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from in idual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen “phylodynamics.” We introduce a phylodynamic framework for the dissection of dynamic forces that determine the ersity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.
Publisher: American Society for Microbiology
Date: 15-10-2006
DOI: 10.1128/JVI.00441-06
Abstract: The ubiquitous human polyomavirus JC (JCV) is a small double-stranded DNA virus that establishes a persistent infection, and it is often transmitted from parents to children. There are at least 14 subtypes of the virus associated with different human populations. Because of its presumed co ergence with humans, JCV has been used as a genetic marker for human evolution and migration. Co ergence has also been used as a basis for estimating the rate of nucleotide substitution in JCV. We tested the hypothesis of host-virus co ergence by (i) performing a reconciliation analysis of phylogenetic trees of human and JCV populations and (ii) providing the first estimate of the evolutionary rate of JCV that is independent from the assumption of co ergence. Strikingly, our comparisons of JCV and human phylogenies provided no evidence for co ergence, suggesting that this virus should not be used as a marker for human population history. Further, while the estimated nucleotide substitution rate of JCV has large confidence intervals due to limited s ling, our analysis suggests that this virus may evolve nearly two orders of magnitude faster than predicted under the co ergence hypothesis.
Publisher: Oxford University Press (OUP)
Date: 16-03-2011
Publisher: American Society for Microbiology
Date: 04-2004
DOI: 10.1128/JVI.78.7.3447-3454.2004
Abstract: Hepatitis C virus (HCV) persists in the majority of those infected despite host immune responses. Evidence has accrued that selectively fixed mutations in the envelope genes (E1 and E2) are associated with viral persistence, particularly those that occur within the first hypervariable region of E2 (HVR1). However, the in idual amino acid residues under selection have not been identified, nor have their selection pressures been measured, despite the importance of this information for understanding disease pathogenesis and for vaccine design. We performed a high-resolution analysis of published gene sequence data from in iduals undergoing acute HCV infection, employing two phylogenetic methods to determine site-specific selection pressures. Strikingly, we found a statistically significant association between the number of sites selected and disease outcome, with the fewest selected sites in fulminant HCV cases and the greatest number of selected sites in rapid progressors, reflecting the duration and intensity of the arms race between host and virus. Moreover, sites outside the HVR1 appear to play a major role in viral evolution and pathogenesis, although there was no association between viral persistence and specific mutations in E1 and E2. Our analysis therefore allows fine dissection of immune selection pressures, which may be more erse than previously thought. Such analyses could play a similarly informative role in studies of other persistent virus infections, such as human immunodeficiency virus.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2015
Publisher: Springer Science and Business Media LLC
Date: 04-2003
DOI: 10.1038/422679A
Publisher: Springer Science and Business Media LLC
Date: 13-12-2018
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.MEEGID.2004.06.011
Abstract: The human immunodeficiency virus (HIV) pandemic continues to grow at an alarming rate, with a further 5 million new infections in 2003. Some 3.5 million of these were in sub-Saharan Africa, where approximately 70% of the world's HIV-positive population resides. In contrast, the spread of HIV in high-income countries has slowed since its discovery in the 1980s, and in regions such as Western Europe prevalence has decreased. Here, we employ coalescent methods to compare the epidemic growth rates of two subtypes of HIV-1 with differing epidemiological profiles: subtype C, which is dominant in sub-Saharan Africa and associated with heterosexual transmission, and subtype B, the main cause of AIDS in Western Europe and North America, and which was primarily transmitted through homosexual sex and injecting drug use. We show that although both subtypes emerged at approximately the same time ( approximately 1960), they have widely differing patterns of exponential population growth. At its current growth rate the epidemic of subtype C in sub-Saharan Africa is doubling every 2.4 years, which is approximately half the rate observed during the early stages of the subtype B epidemic in Western Europe and North America. However, the subtype C growth rate is still 5-10 times greater than that estimated for the blood-borne hepatitis C virus, supporting the hypothesis that sexual transmission has been primarily responsible for the HIV epidemic in sub-Saharan Africa.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 23-04-2021
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.MEEGID.2004.08.001
Abstract: Given the economic and health costs of hepatitis C virus (HCV) infection, and the ongoing transmission within the injecting drug user (IDU) population, there is a need for improved understanding of HCV epidemiology within this risk group. We employed a recently developed method based on phylogenetic analysis to infer HCV epidemic history and to provide the first estimates of the rate of spread of subtypes 1a and 3a circulating within injecting drug user populations. The data indicates that HCV subtype 1a entered the IDU population on at least three separate occasions. Both subtypes demonstrate exponential population growth during the 20th century, with a doubling time of 7-8 years. The results provide a baseline for prediction of the future course of the HCV epidemic, and its likely response to transmission control policies.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2009
DOI: 10.1038/NATURE07746
Publisher: Microbiology Society
Date: 06-2002
DOI: 10.1099/0022-1317-83-6-1419
Abstract: We compared the extent of positive selection acting on acute and persistent strains of measles virus (MV). Far stronger positive selection was found in the fusion (F) and haemagglutinin (H) genes from subacute sclerosing panencephalitis (SSPE) compared to acute MV cases. Most of the positively selected sites identified in these surface glycoprotein genes from SSPE cases correspond to structural, functional or antigenic areas, and could not be explained by the effects of cell passaging. The correlations between selected sites and functional studies of MV are discussed in detail with reference to the maintenance of persistent infection. No positive selection was found in the matrix (M) gene from acute cases of MV and the effects of including hypermutated SSPE M gene sequences in phylogenetic inference were also explored. Finally, using H gene data, we estimated the rate of molecular evolution for SSPE strains as 3·4×10 −4 substitutions/site/year, which is similar to previous estimates obtained for acute strains.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2019
DOI: 10.1038/S41564-019-0440-7
Abstract: This Article was mistakenly not made Open Access when originally published this has now been amended, and information about the Creative Commons Attribution 4.0 International License has been added into the ‘Additional information’ section.
Publisher: Springer Science and Business Media LLC
Date: 04-2017
DOI: 10.1038/NATURE22040
Publisher: Elsevier BV
Date: 2021
Publisher: Oxford University Press (OUP)
Date: 07-2018
DOI: 10.1093/VE/VEY025
Publisher: Springer Science and Business Media LLC
Date: 21-03-2019
DOI: 10.1038/S41564-019-0429-2
Abstract: In the version of this Article originally published, the affiliation for author Catherine Linard was incorrectly stated as ‘ 6 Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK’. The correct affiliation is ‘ 9 Spatial Epidemiology Lab (SpELL), Universite Libre de Bruxelles, Brussels, Belgium’. The affiliation for author Hongjie Yu was also incorrectly stated as ‘ 11 Department of Statistics, Harvard University, Cambridge, MA, USA’. The correct affiliation is ‘ 15 School of Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China’. This has now been amended in all versions of the Article.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2017
DOI: 10.1038/NATURE22401
Publisher: American Society for Microbiology
Date: 02-2010
DOI: 10.1128/JVI.02512-09
Publisher: American Association for the Advancement of Science (AAAS)
Date: 21-05-2021
Abstract: Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from Sã o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response. Science , abh1558 and abh2644, this issue p. 821 and p. 815
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-09-2021
Abstract: A triumph that has emerged from the catastrophe of the severe acute respiratory syndrome coronavirus 2 pandemic has been the rapid development of several potent vaccines. However, 18 months into the pandemic and more than 6 months after vaccine approval, wealthy countries remain the major beneficiaries. Wagner et al . model the consequences of vaccine stockpiling in affluent countries on disease rates in lower- and middle-income countries and the consequences for the eruption of new variants that could jeopardize the early success of vaccines. For countries that can readily access vaccines, it would be better to share vaccines equitably to lower disease burdens in countries with less access, reduce the cost of having to be constantly vigilant for case imports, and minimize virus evolution. —CA
Publisher: Wiley
Date: 03-09-2015
DOI: 10.1002/JMV.24069
Abstract: HCV strains belonging to genotype 4 may be gaining endemicity across Continental Europe but the extent of their spread in the United Kingdom is unknown. Sera referred from patients attending hospitals in England between 2004 through 2008 were characterised. A total of 243 sera carried HCV genotype 4. The most common subtypes were 4a (33%) and 4d (35%). Compared to patients infected by 4d, those infected by 4a were 20 times more likely to be Middle Eastern than English, and those infected by non-4a/4d were older, tended to be female, and 50 or 12 times more likely to be Middle Eastern or South Asian, respectively, than English. Persons infected by 4d tended to be English rather than Middle Eastern or South Asian. One group of 4d strains clustered with strains reported from persons in Europe engaged in male homosexual activity. Surveillance of trends in the importation and subsequent spread of HCV genotype 4 and its subtypes is advocated.
Publisher: Wiley
Date: 11-05-2012
Publisher: Microbiology Society
Date: 04-2012
Abstract: GII.4 noroviruses are a major cause of acute gastroenteritis in humans. A new variant of GII.4, the 2008 variant, has recently increased its prevalence on a global scale. A previous study of this variant in Japan suggested that it might be of recombinant origin, with a breakpoint at the ORF1–ORF2 junction. Here, examination of the evolutionary origin of the 2008 variant based on a larger s le of worldwide GII.4 norovirus sequences revealed a more complex pattern of recombination between the 2006a- and 2006b-like variants of genotype GII.4, involving the P2 antigenic domain. Double (termed ‘2008i’) and triple (termed ‘2008ii’) recombinant forms of 2008 variants were identified. This study highlights the possible importance of intra-genotypic recombination over antigenic regions in driving norovirus evolution, and is suggestive of a process analogous to the antigenic shift of influenza A virus by reassortment.
Publisher: Springer Science and Business Media LLC
Date: 05-2011
DOI: 10.1038/NATURE10004
Abstract: Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has h ered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic s les collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12 years of systematic surveillance in this region, supplemented with data stretching back 34 years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically erse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Public Library of Science (PLoS)
Date: 22-08-2023
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 04-2016
Publisher: Cold Spring Harbor Laboratory
Date: 26-08-2021
DOI: 10.1101/2021.08.21.21262393
Abstract: Genomic sequencing provides critical information to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments and vaccines, and guide public health responses. To investigate the spatiotemporal heterogeneity in the global SARS-CoV-2 genomic surveillance, we estimated the impact of sequencing intensity and turnaround times (TAT) on variant detection in 167 countries. Most countries submit genomes days after s le collection, and 77% of low and middle income countries sequenced .5% of their cases. We found that sequencing at least 0.5% of the cases, with a TAT days, could be a benchmark for SARS-CoV-2 genomic surveillance efforts. Socioeconomic inequalities substantially impact our ability to quickly detect SARS-CoV-2 variants, and undermine the global pandemic preparedness. Socioeconomic inequalities impacted the SARS-CoV-2 genomic surveillance, and undermined the global pandemic preparedness.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2019
DOI: 10.1038/S41564-019-0376-Y
Abstract: The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus . The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.
Publisher: American Society for Microbiology
Date: 23-02-2017
Abstract: Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, EcEs062_16 and EcEs089_16, isolated from the sera of febrile patients in Esmeraldas City, in the northern coastal province of Esmeraldas, Ecuador, in April 2016. These are the first complete ZIKV genomes to be reported from Ecuador.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2021
Publisher: American Association for the Advancement of Science (AAAS)
Date: 15-01-2021
Abstract: Advances in experimental approaches for single-cell analysis allow in situ sequencing, genomic barcoding, and mapping of cell lineages within tissues and organisms. Large amounts of data have thus accumulated and present an analytical challenge. Stadler et al. recognized the need for conceptual and computational approaches to fully exploit these technological advances for the understanding of normal and disease states. The authors review ideas taken from phylodynamics of infectious disease and show how similar tree-building techniques can be applied to monitoring changes in somatic cell lineages for applications ranging from development and differentiation to cancer biology. Science , this issue p. eaah6266
Publisher: Oxford University Press (OUP)
Date: 04-12-2009
Publisher: Oxford University Press (OUP)
Date: 2016
DOI: 10.1093/VE/VEW016
Publisher: Springer Science and Business Media LLC
Date: 29-01-2021
Publisher: Oxford University Press (OUP)
Date: 30-07-2021
DOI: 10.1093/VE/VEAB064
Abstract: The response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the ‘real-time’ generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic’s transmission lineages.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2008
DOI: 10.1038/NATURE06945
Publisher: Oxford University Press (OUP)
Date: 07-2022
DOI: 10.1093/VE/VEAC074
Abstract: Avian influenza A virus (AIV) is ubiquitous in waterfowl and is detected annually at high prevalence in waterfowl during the Northern Hemisphere autumn. Some AIV subtypes are globally common in waterfowl, such as H3N8, H4N6, and H6N2, and are detected in the same populations at a high frequency, annually. In order to investigate genetic features associated to the long-term maintenance of common subtypes in migratory ducks, we sequenced 248 H4 viruses isolated across 8 years (2002–9) from mallards (Anas platyrhynchos) s led in southeast Sweden. Phylogenetic analyses showed that both H4 and N6 sequences fell into three distinct lineages, structured by year of isolation. Specifically, across the 8 years of the study, we observed lineage replacement, whereby a different HA lineage circulated in the population each year. Analysis of deduced amino acid sequences of the HA lineages illustrated key differences in regions of the globular head of hemagglutinin that overlap with established antigenic sites in homologous hemagglutinin H3, suggesting the possibility of antigenic differences among these HA lineages. Beyond HA, lineage replacement was common to all segments, such that novel genome constellations were detected across years. A dominant genome constellation would rapidly lify in the duck population, followed by unlinking of gene segments as a result of reassortment within 2–3 weeks following introduction. These data help reveal the evolutionary dynamics exhibited by AIV on both annual and decadal scales in an important reservoir host.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2013
DOI: 10.1038/NATURE12515
Publisher: Oxford University Press (OUP)
Date: 11-2006
DOI: 10.1534/GENETICS.105.052019
Abstract: The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic ersity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences s led longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.
Publisher: Elsevier BV
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 02-2002
DOI: 10.1007/S00239-001-0064-3
Abstract: The study of rates of nucleotide substitution in RNA viruses is central to our understanding of their evolution. Herein we report a comprehensive analysis of substitution rates in 50 RNA viruses using a recently developed maximum likelihood phylogenetic method. This analysis revealed a significant relationship between genetic ergence and isolation time for an extensive array of RNA viruses, although more rate variation was usually present among lineages than would be expected under the constraints of a molecular clock. Despite the lack of a molecular clock, the range of statistically significant variation in overall substitution rates was surprisingly narrow for those viruses where a significant relationship between genetic ergence and time was found, as was the case when synonymous sites were considered alone, where the molecular clock was rejected less frequently. An analysis of the ecological and genetic factors that might explain this rate variation revealed some evidence of significantly lower substitution rates in vector-borne viruses, as well as a weak correlation between rate and genome length. Finally, a simulation study revealed that our maximum likelihood estimates of substitution rates are valid, even if the molecular clock is rejected, provided that sufficiently large data sets are analyzed.
Publisher: Springer Science and Business Media LLC
Date: 04-2001
DOI: 10.1038/35074179
Publisher: American Association for the Advancement of Science (AAAS)
Date: 22-06-2001
Abstract: Hepatitis C virus (HCV) is a leading worldwide cause of liver disease. Here, we use a new model of HCV spread to investigate the epidemic behavior of the virus and to estimate its basic reproductive number from gene sequence data. We find significant differences in epidemic behavior among HCV subtypes and suggest that these differences are largely the result of subtype-specific transmission patterns. Our model builds a bridge between the disciplines of population genetics and mathematical epidemiology by using pathogen gene sequences to infer the population dynamic history of an infectious disease.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-09-2020
Abstract: Brazil has been hard-hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Candido et al. combined genomic and epidemiological analyses to investigate the impact of nonpharmaceutical interventions (NPIs) in the country. By setting up a network of genomic laboratories using harmonized protocols, the researchers found a 29% positive rate for SARS-CoV-2 among collected s les. More than 100 international introductions of SARS-CoV-2 into Brazil were identified, including three clades introduced from Europe that were already well established before the implementation of NPIs and travel bans. The virus spread from urban centers to the rest of the country, along with a 25% increase in the average distance traveled by air passengers before travel bans, despite an overall drop in short-haul travel. Unfortunately, the evidence confirms that current interventions remain insufficient to keep virus transmission under control in Brazil. Science , this issue p. 1255
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2020
DOI: 10.1101/2020.06.11.20128249
Abstract: Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Due to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus transmission and epidemic spread remain challenging. We investigate the impact of NPIs in Brazil using epidemiological, mobility and genomic data. Mobility-driven transmission models for São Paulo and Rio de Janeiro cities show that the reproduction number ( R t ) reached below 1 following NPIs but slowly increased to values between 1 to 1.3 (1.0–1.6). Genome sequencing of 427 new genomes and analysis of a geographically representative genomic dataset from 21 of the 27 Brazilian states identified international introductions of SARS-CoV-2 in Brazil. We estimate that three clades introduced from Europe emerged between 22 and 27 February 2020, and were already well-established before the implementation of NPIs and travel bans. During this first phase of the epidemic establishment of SARS-CoV-2 in Brazil, we find that the virus spread mostly locally and within-state borders. Despite sharp decreases in national air travel during this period, we detected a 25% increase in the average distance travelled by air passengers during this time period. This coincided with the spread of SARS-CoV-2 from large urban centers to the rest of the country. In conclusion, our results shed light on the role of large and highly connected populated centres in the rapid ignition and establishment of SARS-CoV-2, and provide evidence that current interventions remain insufficient to keep virus transmission under control in Brazil. Joint analysis of genomic, mobility and epidemiological novel data provide unique insight into the spread and transmission of the rapidly evolving epidemic of SARS-CoV-2 in Brazil.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2019
DOI: 10.1038/S41598-019-41192-3
Abstract: Human mobility is an important driver of geographic spread of infectious pathogens. Detailed information about human movements during outbreaks are, however, difficult to obtain and may not be available during future epidemics. The Ebola virus disease (EVD) outbreak in West Africa between 2014–16 demonstrated how quickly pathogens can spread to large urban centers following one cross-species transmission event. Here we describe a flexible transmission model to test the utility of generalised human movement models in estimating EVD cases and spatial spread over the course of the outbreak. A transmission model that includes a general model of human mobility significantly improves prediction of EVD’s incidence compared to models without this component. Human movement plays an important role not only to ignite the epidemic in locations previously disease free, but over the course of the entire epidemic. We also demonstrate important differences between countries in population mixing and the improved prediction attributable to movement metrics. Given their relative rareness, locally derived mobility data are unlikely to exist in advance of future epidemics or pandemics. Our findings show that transmission patterns derived from general human movement models can improve forecasts of spatio-temporal transmission patterns in places where local mobility data is unavailable.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 29-09-2014
DOI: 10.1002/HEP.27310
Publisher: Springer Science and Business Media LLC
Date: 15-07-2020
Publisher: Oxford University Press (OUP)
Date: 11-01-2007
Abstract: Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.
Publisher: Elsevier BV
Date: 05-2009
Publisher: Elsevier BV
Date: 06-2018
Publisher: Oxford University Press (OUP)
Date: 14-06-2006
Abstract: RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.
Publisher: Research Square Platform LLC
Date: 19-05-2021
DOI: 10.21203/RS.3.RS-520627/V1
Abstract: Understanding the drivers for spread of SARS-CoV-2 in higher education settings is important to limit transmission between students, and onward spread into at-risk populations. In this study, we prospectively sequenced 482 SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge from 5 October to 6 December 2020. We performed a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. After a limited number of viral introductions into the university, the majority of student cases were linked to a single genetic cluster, likely dispersed across the university following social gatherings at a venue outside the university. We identified considerable onward transmission associated with student accommodation and courses this was effectively contained using local infection control measures and dramatically reduced following a national lockdown. We observed that transmission clusters were largely segregated within the university or within the community. This study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Oliver Pybus.