scholarly journals Fitness Estimation for Viral Variants in the Context of Cellular Coinfection

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1216
Author(s):  
Huisheng Zhu ◽  
Brent Allman ◽  
Katia Koelle
Keyword(s):  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Population Level ◽  
Viral Fitness ◽  
Fitness Effects ◽  
Fitness Advantage ◽  
Viral Adaptation ◽  
Zoonotic Viruses ◽  
Frequency Changes

Animal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host’s infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.

scholarly journals Fitness estimation for viral variants in the context of cellular coinfection

2021 ◽  
Author(s):  
Huisheng Zhu ◽  
Brent E Allman ◽  
Katia Koelle
Keyword(s):  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Population Level ◽  
Viral Fitness ◽  
Fitness Effects ◽  
Fitness Advantage ◽  
Viral Adaptation ◽  
Zoonotic Viruses ◽  
Frequency Changes

AbstractAnimal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host’s infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally-sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.

scholarly journals Stochastic processes dominate the within and between host evolution of influenza virus

2017 ◽  
Author(s):  
John T. McCrone ◽  
Robert J. Woods ◽  
Emily T. Martin ◽  
Ryan E. Malosh ◽  
Arnold S. Monto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Stochastic Processes ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Influenza A Viruses ◽  
Effective Population ◽  
The Individual ◽  
Host Evolution

AbstractThe global evolutionary dynamics of influenza virus ultimately derive from processes that take place within and between infected individuals. Here we define the dynamics of influenza A virus populations in human hosts through next generation sequencing of 249 specimens from 200 individuals collected over 6290 person-seasons of observation. Because these viruses were collected over 5 seasons from individuals in a prospective community-based cohort, they are broadly representative of natural human infections with seasonal viruses. We used viral sequence data from 35 serially sampled individuals to estimate a within host effective population size of 30-70 and an in vivo mutation rate of 4x10−5 per nucleotide per cellular infectious cycle. These estimates are consistent across several models and robust to the models' underlying assumptions. We also identified 43 epidemiologically linked and genetically validated transmission pairs. Maximum likelihood optimization of multiple transmission models estimates an effective transmission bottleneck of 1-2 distinct genomes. Our data suggest that positive selection of novel viral variants is inefficient at the level of the individual host and that genetic drift and other stochastic processes dominate the within and between host evolution of influenza A viruses.

scholarly journals Co-evolution networks of HIV/HCV are modular with direct association to structure and function

2018 ◽  
Author(s):  
Ahmed Abdul Quadeer ◽  
David Morales-Jimenez ◽  
Matthew R. McKay
Keyword(s):  
Statistical Method ◽  
Immune Escape ◽  
Sequence Data ◽  
Principal Component ◽  
Population Level ◽  
Viral Fitness ◽  
Sparse Principal Component Analysis ◽  
Phenotypic Properties ◽  
Structural And Functional Properties ◽  
Robust Statistical Method

AbstractMutational correlation patterns found in population-level sequence data for the Human Immunodeficiency Virus (HIV) and the Hepatitis C Virus (HCV) have been demonstrated to be informative of viral fitness. Such patterns can be seen as footprints of the intrinsic functional constraints placed on viral evolution under diverse selective pressures. Here, considering multiple HIV and HCV proteins, we demonstrate that these mutational correlations encode a modular co-evolutionary structure that is tightly linked to the structural and functional properties of the respective proteins. Specifically, by introducing a robust statistical method based on sparse principal component analysis, we identify near-disjoint sets of collectively-correlated residues (sectors) having mostly a one-to-one association to largely distinct structural or functional domains. This suggests that the distinct phenotypic properties of HIV/HCV proteins often give rise to quasi-independent modes of evolution, with each mode involving a sparse and localized network of mutational interactions. Moreover, individual inferred sectors of HIV are shown to carry immunological significance, providing insight for guiding targeted vaccine strategies.Author summaryHIV and HCV cause devastating infectious diseases for which no functional vaccine exists. A key problem is that while immune cells may induce individual mutations that compromise viral fitness, this is typically restored through other “compensatory” mutations, leading to immune escape. These compensatory pathways are complicated and remain poorly understood. They do, however, leave co-evolutionary markers which may be inferred from measured sequence data. Here, by introducing a new robust statistical method, we demonstrated that the compensatory networks employed by both viruses exhibit a remarkably simple decomposition involving small and near-distinct groups of protein residues, with most groups having a clear association to biological function or structure. This provides insights that can be harnessed for the purpose of vaccine design.

scholarly journals A Single Codon in the Nucleocapsid Protein C Terminus Contributes to In Vitro and In Vivo Fitness of Edmonston Measles Virus

2006 ◽  
Vol 80 (6) ◽  
pp. 2904-2912 ◽  
Author(s):  
Thomas Carsillo ◽  
Xinsheng Zhang ◽  
Daphne Vasconcelos ◽  
Stefan Niewiesk ◽  
Michael Oglesbee
Keyword(s):  
Nucleocapsid Protein ◽  
Measles Virus ◽  
Neuroblastoma Cells ◽  
Viral Fitness ◽  
Single Amino Acid ◽  
Genome Replication ◽  
Fitness Advantage ◽  
C Terminus

ABSTRACT The major inducible 70-kDa heat shock protein (hsp72) increases measles virus (MV) transcription and genome replication. This stimulatory effect is attributed to hsp72 interaction with two highly conserved hydrophobic domains in the nucleocapsid protein (N) C terminus of Edmonston MV. These domains are known as Box-2 and Box-3. A single amino acid substitution in Box-3 of Edmonston MV (i.e., N522D) disrupts hsp72 binding. The prevalence of the N522D substitution in contemporary wild-type MV isolates suggests that this sequence has been positively selected. The present work determined if the N522D substitution enhances viral fitness and the degree to which any fitness advantage is influenced by hsp72 levels. Both parent Edmonston MV (Ed N) and an N522D substitution mutant (Ed N-522D) exhibited similar growth on Vero and murine neuroblastoma cells and in cotton rat lung, although Ed N-522D virus exhibited an attenuated in vitro response to hsp72 overexpression. In contrast, mixed infections showed a significantly reduced in vitro and in vivo fitness of Ed N-522D virus. Results support the involvement of additional selectional pressures that maintain the circulation of virus containing N-522D despite the cost to viral fitness.

scholarly journals The effective population size and mutation rate of influenza A virus in acutely infected individuals

2020 ◽  
Author(s):  
John T. McCrone ◽  
Robert J. Woods ◽  
Arnold S. Monto ◽  
Emily T. Martin ◽  
Adam S. Lauring
Keyword(s):  
Population Size ◽  
Effective Population Size ◽  
Mutation Rate ◽  
Influenza A ◽  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Effective Population

AbstractThe global evolutionary dynamics of influenza viruses ultimately derive from processes that take place within and between infected individuals. Recent work suggests that within-host populations are dynamic, but an in vivo estimate of mutation rate and population size in naturally infected individuals remains elusive. Here we model the within-host dynamics of influenza A viruses using high depth of coverage sequence data from 200 acute infections in an outpatient, community setting. Using a Wright-Fisher model, we estimate a within-host effective population size of 32-72 and an in vivo mutation rate of 3.4×10−6 per nucleotide per generation.

scholarly journals The population genomics of transposable element activation in the highly repressive genome of an agricultural pathogen

2020 ◽  
Author(s):  
Danilo Pereira ◽  
Ursula Oggenfuss ◽  
Bruce A. McDonald ◽  
Daniel Croll
Keyword(s):  
Genetic Diversity ◽  
Transposable Elements ◽  
Evolutionary Dynamics ◽  
Population Genomics ◽  
Sequence Data ◽  
Demographic History ◽  
Purifying Selection ◽  
Population Level ◽  
Wide Range ◽  
Genome Analyses

AbstractThe activity of transposable elements (TEs) can be an important driver of genetic diversity with TE-mediated mutations having a wide range of fitness consequences. To avoid deleterious effects of TE activity, some fungi evolved highly sophisticated genomic defences to reduce TE proliferation across the genome. Repeat-induced point (RIP) mutations is a fungal-specific TE defence mechanism efficiently targeting duplicated sequences. The rapid accumulation of RIP mutations is expected to deactivate TEs over the course of a few generations. The evolutionary dynamics of TEs at the population level in a species with highly repressive genome defences is poorly understood. Here, we analyze 366 whole-genome sequences of Parastagonospora nodorum, a fungal pathogen of wheat with efficient RIP. A global population genomics analysis revealed high levels of genetic diversity and signs of frequent sexual recombination. Contrary to expectations for a species with RIP, we identified recent TE activity in multiple populations. The TE composition and copy numbers showed little divergence among global populations regardless of the demographic history. Miniature inverted-repeat transposable elements (MITEs) and terminal repeat retrotransposons in miniature (TRIMs) were largely underlying recent intra-species TE expansions. We inferred RIP footprints in individual TE families and found that recently active, high-copy TEs have possibly evaded genomic defences. We find no evidence that recent positive selection acted on TE-mediated mutations rather that purifying selection maintained new TE insertions at low insertion frequencies in populations. Our findings highlight the complex evolutionary equilibria established by the joint action of TE activity, selection and genomic repression.Data SummaryAll Illumina sequence data is available from the NCBI SRA BioProject numbers PRJNA606320, PRJNA398070 and PRJNA476481 (https://www.ncbi.nlm.nih.gov/bioproject). The Methods and Supplementary Figures S1-S11 and Supplementary Tables S1-S4 provide all information on strain locations and outcomes of genome analyses.

scholarly journals POPULATION GENETICS OF DROSOPHILA AMYLASE. V. GENETIC BACKGROUND AND SELECTION ON DIFFERENT CARBOHYDRATES

Genetics ◽  
1984 ◽  
Vol 106 (4) ◽  
pp. 625-629
Author(s):  
Jeffrey R Powell ◽  
George D Amato
Keyword(s):  
Genetic Background ◽  
Evolutionary Dynamics ◽  
Sequence Data ◽  
Drosophila Pseudoobscura ◽  
Gene Variants ◽  
Specific Expression ◽  
Carbohydrate Source ◽  
Dna Sequence Data ◽  
Laboratory Populations ◽  
Frequency Changes

ABSTRACT Frequency changes in amylase allozymes and patterns of tissue-specific expression of amylase have been monitored in laboratory populations of Drosophila pseudoobscura maintained on media in which the only carbohydrate source was maltose or starch. Nonrandom changes occurred in patterns of expression, whereas no patterns in allozyme frequency changes were discernible. The nature of the pattern changes was similar to an identical study done on populations derived from a natural population several hundred miles from the population used in the present experiments. However, in the previous study nonrandom changes in allozyme frequencies were also noted. Evidently, selection on the Drosophila amylase system differs depending upon the genetic background of the population. Furthermore, the evolutionary dynamics of structural gene variants and those regions controlling its expression may be independent, a result consistent with DNA sequence data.

scholarly journals Long-Term Cocirculation of Two Strains of Pepino Mosaic Virus in Tomato Crops and Its Effect on Population Genetic Variability

2020 ◽  
Vol 110 (1) ◽  
pp. 49-57 ◽  
Author(s):  
C. Alcaide ◽  
M. P. Rabadán ◽  
M. Juárez ◽  
P. Gómez
Keyword(s):  
Genetic Variability ◽  
Mosaic Virus ◽  
Evolutionary Dynamics ◽  
Geographical Area ◽  
Viral Fitness ◽  
Mixed Infections ◽  
Supporting Evidence ◽  
Pepino Mosaic Virus ◽  
Nucleotide Variability

Mixed viral infections are common in plants, and the evolutionary dynamics of viral populations may differ depending on whether the infection is caused by single or multiple viral strains. However, comparative studies of single and mixed infections using viral populations in comparable agricultural and geographical locations are lacking. Here, we monitored the occurrence of pepino mosaic virus (PepMV) in tomato crops in two major tomato-producing areas in Murcia (southeastern Spain), supporting evidence showing that PepMV disease-affected plants had single infections of the Chilean 2 (CH2) strain in one area and the other area exhibited long-term (13 years) coexistence of the CH2 and European (EU) strains. We hypothesized that circulating strains of PepMV might be modulating the differentiation between them and shaping the evolutionary dynamics of PepMV populations. Our phylogenetic analysis of 106 CH2 isolates randomly selected from both areas showed a remarkable divergence between the CH2 isolates, with increased nucleotide variability in the geographical area where both strains cocirculate. Furthermore, the potential virus–virus interaction was studied further by constructing six full-length infectious CH2 clones from both areas, and assessing their viral fitness in the presence and absence of an EU-type isolate. All CH2 clones showed decreased fitness in mixed infections and although complete genome sequencing indicated a nucleotide divergence of those CH2 clones by area, the magnitude of the fitness response was irrespective of the CH2 origin. Overall, these results suggest that although agroecological cropping practices may be particularly important for explaining the evolutionary dynamics of PepMV in tomato crops, the cocirculation of both strains may have implications on the genetic variability of PepMV populations.

scholarly journals Protective population behavior change in outbreaks of emerging infectious disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Evans K. Lodge ◽  
Annakate M. Schatz ◽  
John M. Drake
Keyword(s):  
Behavior Change ◽  
Ebola Virus ◽  
Virus Disease ◽  
Population Level ◽  
Emerging Infections ◽  
Emerging Pathogens ◽  
Susceptible Population ◽  
Zoonotic Infections ◽  
Zoonotic Viruses ◽  
And Behavior

Abstract Background During outbreaks of emerging and re-emerging infections, the lack of effective drugs and vaccines increases reliance on non-pharmacologic public health interventions and behavior change to limit human-to-human transmission. Interventions that increase the speed with which infected individuals remove themselves from the susceptible population are paramount, particularly isolation and hospitalization. Ebola virus disease (EVD), Severe Acute Respiratory Syndrome (SARS), and Middle East Respiratory Syndrome (MERS) are zoonotic viruses that have caused significant recent outbreaks with sustained human-to-human transmission. Methods This investigation quantified changing mean removal rates (MRR) and days from symptom onset to hospitalization (DSOH) of infected individuals from the population in seven different outbreaks of EVD, SARS, and MERS, to test for statistically significant differences in these metrics between outbreaks. Results We found that epidemic week and viral serial interval were correlated with the speed with which populations developed and maintained health behaviors in each outbreak. Conclusions These findings highlight intrinsic population-level changes in isolation rates in multiple epidemics of three zoonotic infections with established human-to-human transmission and significant morbidity and mortality. These data are particularly useful for disease modelers seeking to forecast the spread of emerging pathogens.

scholarly journals Reconsideration of the ‘well-known’ hypotrichous ciliate Pleurotricha curdsi (Shi et al., 2002) Gupta et al., 2003 (Ciliophora, Sporadotrichida), with notes on its morphology, morphogenesis and molecular phylogeny

2015 ◽  
Vol 65 (Pt_9) ◽  
pp. 3216-3225 ◽  
Author(s):  
Xiaoteng Lu ◽  
Chen Shao ◽  
Yuhe Yu ◽  
Alan Warren ◽  
Jie Huang
Keyword(s):  
Sequence Data ◽  
Southern China ◽  
Phylogenetic Analyses ◽  
Large Body ◽  
Small Subunit ◽  
Variable Number ◽  
Ssu Rdna ◽  
Intermediate Form ◽  
Rdna Sequence Data

The oxytrichid species Pleurotricha curdsi (Shi et al., 2002) Gupta et al., 2003, isolated from a tributary of the Yangtze River in the Mudong district of Chongqing, southern China, was reinvestigated with emphasis on its morphology, morphogenesis and small-subunit (SSU) rDNA-based phylogeny. Compared with three previously described populations, the Mudong population of P. curdsi is characterized by its large body size, 170–295 × 65–110 μm in vivo, and by having a variable number of right marginal rows, either two or three. Likewise, the number of right marginal rows anlagen (RMA) is also variable, i.e. usually two, but sometimes several small extra anlagen that give rise to the formation of the third row, are present to the left of the RMAs. We posit that the Mudong population is an intermediate form between the three previously described populations. Phylogenetic analyses based on the SSU rDNA sequence data show that all populations of P. curdsi cluster with the type species of the genus, Pleurotricha lanceolata, in a clade nested within the Oxytrichidae.

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