scholarly journals Molecular Evolutionary Dynamics of Respiratory Syncytial Virus Group A in Recurrent Epidemics in Coastal Kenya

2016 ◽  
Vol 90 (10) ◽  
pp. 4990-5002 ◽  
Author(s):  
James R. Otieno ◽  
Charles N. Agoti ◽  
Caroline W. Gitahi ◽  
Ann Bett ◽  
Mwanajuma Ngama ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Respiratory Syncytial Virus ◽  
Time Scales ◽  
Evolutionary Dynamics ◽  
Nucleotide Substitutions ◽  
High Genetic Diversity ◽  
Data Set ◽  
New Variant ◽  
Syncytial Virus ◽  
Highest Posterior Density

ABSTRACTThe characteristic recurrent epidemics of human respiratory syncytial virus (RSV) within communities may result from the genetic variability of the virus and associated evolutionary adaptation, reducing the efficiency of preexisting immune responses. We analyzed the molecular evolutionary changes in the attachment (G) glycoprotein of RSV-A viruses collected over 13 epidemic seasons (2000 to 2012) in Kilifi (n= 649), Kenya, and contemporaneous sequences (n= 1,131) collected elsewhere within Kenya and 28 other countries. Genetic diversity in the G gene in Kilifi was dynamic both within and between epidemics, characterized by frequent new variant introductions and limited variant persistence between consecutive epidemics. Four RSV-A genotypes were detected in Kilifi: ON1 (11.9%), GA2 (75.5%), GA5 (12.3%), and GA3 (0.3%), with predominant genotype replacement of GA5 by GA2 and then GA2 by ON1. Within these genotypes, there was considerable variation in potentialN-glycosylation sites, with GA2 and ON1 viruses showing up to 15 different patterns involving eight possible sites. Further, we identified 15 positively selected and 34 genotype-distinguishing codon sites, with six of these sites exhibiting both characteristics. The mean substitution rate of the G ectodomain for the Kilifi data set was estimated at 3.58 × 10−3(95% highest posterior density interval = 3.04 to 4.16) nucleotide substitutions/site/year. Kilifi viruses were interspersed in the global phylogenetic tree, clustering mostly with Kenyan and European sequences. Our findings highlight ongoing genetic evolution and high diversity of circulating RSV-A strains, locally and globally, with potential antigenic differences. Taken together, these provide a possible explanation on the nature of recurrent local RSV epidemics.IMPORTANCEThe mechanisms underlying recurrent epidemics of RSV are poorly understood. We observe high genetic diversity in circulating strains within and between epidemics in both local and global settings. On longer time scales (∼7 years) there is sequential replacement of genotypes, whereas on shorter time scales (one epidemic to the next or within epidemics) there is a high turnover of variants within genotypes. Further, this genetic diversity is predicted to be associated with variation in antigenic profiles. These observations provide an explanation for recurrent RSV epidemics and have potential implications on the long-term effectiveness of vaccines.

scholarly journals Genetic diversity and evolutionary dynamics of respiratory syncytial virus over eleven consecutive years of surveillance in Senegal

2021 ◽  
pp. 104864
Author(s):  
Amary Fall ◽  
Farah Elawar ◽  
Emma B. Hodcroft ◽  
Mamadou Malado Jallow ◽  
Cheikh Talibouya Toure ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Respiratory Syncytial Virus ◽  
Evolutionary Dynamics ◽  
Syncytial Virus

scholarly journals In Vitro and In Vivo Fitness of Respiratory Syncytial Virus Monoclonal Antibody Escape Mutants

2006 ◽  
Vol 80 (23) ◽  
pp. 11651-11657 ◽  
Author(s):  
Xiaodong Zhao ◽  
Enmei Liu ◽  
Fu-Ping Chen ◽  
Wayne M. Sullender
Keyword(s):  
Cell Culture ◽  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Viral Population ◽  
Nucleotide Substitutions ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
In Vivo Growth

ABSTRACT Respiratory syncytial virus (RSV) is the only infectious disease for which a monoclonal antibody (MAb) is used in humans. Palivizumab (PZ) is a humanized murine MAb to the F protein of RSV. PZ-resistant viruses appear after in vitro and in vivo growth of RSV in the presence of PZ. Fitness for replication could be a determinant of the likelihood of dissemination of resistant viruses. We assessed the fitness of two PZ-resistant viruses (F212 and MP4). F212 grew less well in cell culture than the parent A2 virus and was predicted to be less fit than A2. Equal amounts of F212 and A2 were mixed and passaged in cell culture. F212 disappeared from the viral population, indicating it was less fit than the A2 virus. The MP4 virus grew as well as A2 in culture and in cotton rats. A2/MP4 virus input ratios of 1:1, 10:1, 100:1, and 1,000:1 were compared in competitive replication. For all input ratios except 1,000:1, the MP4 virus became dominant, supplanting the A2 virus. The MP4 virus also dominated the A2 virus during growth in cotton rats. Thus, the mutant MP4 virus was more fit than A2 virus in both in vitro and in vivo competitive replication. Whether this fitness difference was due to the identified nucleotide substitutions in the F gene or to mutations elsewhere in the genome is unknown. Understanding the mechanisms by which mutant virus fitness increased or decreased could prove useful for consideration in attenuated vaccine design efforts.

scholarly journals Genetic diversity and evolutionary insights of respiratory syncytial virus A ON1 genotype: global and local transmission dynamics

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Venkata R. Duvvuri ◽  
Andrea Granados ◽  
Paul Rosenfeld ◽  
Justin Bahl ◽  
Alireza Eshaghi ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Respiratory Syncytial Virus ◽  
Transmission Dynamics ◽  
Syncytial Virus ◽  
Global And Local ◽  
Local Transmission

scholarly journals Genetic Variability and Molecular Evolution of the Human Respiratory Syncytial Virus Subgroup B Attachment G Protein

2005 ◽  
Vol 79 (14) ◽  
pp. 9157-9167 ◽  
Author(s):  
Kalina T. Zlateva ◽  
Philippe Lemey ◽  
Elien Moës ◽  
Anne-Mieke Vandamme ◽  
Marc Van Ranst
Keyword(s):  
Respiratory Syncytial Virus ◽  
Genetic Variability ◽  
G Protein ◽  
Antigenic Variation ◽  
Human Respiratory Syncytial Virus ◽  
Recent Common Ancestor ◽  
Nucleotide Substitutions ◽  
Host Immune Responses ◽  
Most Recent Common Ancestor ◽  
Syncytial Virus

ABSTRACT Human respiratory syncytial virus (HRSV) is the most important cause of acute respiratory disease in infants. Two major subgroups (A and B) have been identified based on antigenic differences in the attachment G protein. Antigenic variation between and within the subgroups may contribute to reinfections with these viruses by evading the host immune responses. To investigate the circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed the G protein genetic variability of subgroup B sequences isolated over a 45-year period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to 2004). Our study revealed that the HRSV-B evolutionary rate (1.95 × 10−3 nucleotide substitutions/site/year) is similar to that previously estimated for HRSV-A (1.83 × 10−3 nucleotide substitutions/site/year). However, natural HRSV-B isolates appear to accommodate more drastic changes in their attachment G proteins. The most recent common ancestor of the currently circulating subgroup B strains was estimated to date back to around the year 1949. The divergence between the two major subgroups was calculated to have occurred approximately 350 years ago. Furthermore, we have identified 12 positively selected sites in the G protein ectodomain, suggesting that immune-driven selective pressure operates in certain codon positions. HRSV-A and -B strains have similar phylodynamic patterns: both subgroups are characterized by global spatiotemporal strain dynamics, where the high infectiousness of HRSV permits the rapid geographic spread of novel strain variants.

scholarly journals The effect of population bottleneck size and selective regime on genetic diversity and evolvability in bacteria

2019 ◽  
Author(s):  
Tanita Wein ◽  
Tal Dagan
Keyword(s):  
Genetic Diversity ◽  
Genetic Drift ◽  
Evolutionary Dynamics ◽  
Natural Populations ◽  
Population Bottleneck ◽  
Population Bottlenecks ◽  
High Genetic Diversity ◽  
Temperature Regimes ◽  
Consequent Reduction ◽  
History Of

AbstractPopulation bottlenecks leading to a drastic reduction of the population size are common in the evolutionary dynamics of natural populations; their occurrence is known to have implications for genome evolution due to genetic drift, the consequent reduction in genetic diversity and the rate of adaptation. Nevertheless, an empirical characterization of the effect of population bottleneck size on evolutionary dynamics of bacteria is currently lacking. Here we show that selective conditions have a stronger effect on the evolutionary history of bacteria in comparison to genetic drift following population bottlenecks. We evolved Escherichia coli populations under three different population bottlenecks (small, medium, large) in two temperature regimes (37°C and 20°C). We find a high genetic diversity in the large in comparison to the small bottleneck size. Nonetheless, the cold temperature led to reduced genetic diversity in all bottleneck sizes, hence, the temperature has a stronger effect on the genetic diversity in comparison to the bottleneck size. A comparison of the fitness gain among the evolved populations reveals a similar pattern where the temperature has a significant effect on the fitness. Our study demonstrates that population bottlenecks are an important determinant of the evolvability in bacteria; their consequences depend on the selective conditions and are best understood via their effect on the standing genetic variation.

scholarly journals Evolution of Human Respiratory Syncytial Virus (RSV) over Multiple Seasons in New South Wales, Australia

2018 ◽  
Author(s):  
Francesca Di Giallonardo ◽  
Jen Kok ◽  
Marian Fernandez ◽  
Ian Carter ◽  
Jemma L. Geoghegan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
New South ◽  
New South Wales ◽  
Host Population ◽  
Human Respiratory Syncytial Virus ◽  
Nucleotide Substitutions ◽  
South Wales ◽  
A Genome ◽  
Syncytial Virus ◽  
Tract Infections

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.

scholarly journals Reversion mutations in phosphoprotein P of a codon-pair-deoptimized human respiratory syncytial virus confer increased transcription, immunogenicity, and genetic stability without loss of attenuation

2021 ◽  
Vol 17 (12) ◽  
pp. e1010191
Author(s):  
Jessica W. Chen ◽  
Lijuan Yang ◽  
Celia Santos ◽  
Sergio A. Hassan ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Temperature Sensitivity ◽  
Genetic Stability ◽  
Large Scale ◽  
Selective Pressure ◽  
Human Respiratory Syncytial Virus ◽  
Nucleotide Substitutions ◽  
Functional Efficiency ◽  
Codon Pair ◽  
Syncytial Virus

Recoding viral genomes by introducing numerous synonymous nucleotide substitutions that create suboptimal codon pairs provides new live-attenuated vaccine candidates. Because recoding typically involves a large number of nucleotide substitutions, the risk of de-attenuation is presumed to be low. However, this has not been thoroughly studied. We previously generated human respiratory syncytial virus (RSV) in which the NS1, NS2, N, P, M and SH ORFs were codon-pair deoptimized (CPD) by 695 synonymous nucleotide changes (Min A virus). Min A exhibited a global reduction in transcription and protein synthesis, was restricted for replication in vitro and in vivo, and exhibited moderate temperature sensitivity. Here, we show that under selective pressure by serial passage at progressively increasing temperatures, Min A regained replication fitness and lost its temperature sensitivity. Whole-genome deep sequencing identified numerous missense mutations in several genes, in particular ones accumulating between codons 25 and 34 of the phosphoprotein (P), a polymerase cofactor and chaperone. When re-introduced into Min A, these P mutations restored viral transcription to wt level, resulting in increased protein expression and RNA replication. Molecular dynamic simulations suggested that these P mutations increased the flexibility of the N-terminal domain of P, which might facilitate its interaction with the nucleoprotein N, and increase the functional efficiency of the RSV transcription/replication complex. Finally, we evaluated the effect of the P mutations on Min A replication and immunogenicity in hamsters. Mutation P[F28V] paradoxically reduced Min A replication but not its immunogenicity. The further addition of one missense mutation each in M and L generated a version of Min A with increased genetic stability. Thus, this study provides further insight into the adaptability of large-scale recoded RNA viruses under selective pressure and identified an improved CPD RSV vaccine candidate.

scholarly journals Evolutionary Dynamics in the RNA Bacteriophage Qβ Depends on the Pattern of Change in Selective Pressures

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 80 ◽  
Author(s):  
Pilar Somovilla ◽  
Susanna Manrubia ◽  
Ester Lázaro
Keyword(s):  
Genetic Diversity ◽  
Temperature Change ◽  
Evolutionary Dynamics ◽  
Environmental Changes ◽  
Evolutionary Process ◽  
Rate Of Change ◽  
High Genetic Diversity ◽  
Adaptive Mutations ◽  
Beneficial Effects ◽  
Selective Pressures

The rate of change in selective pressures is one of the main factors that determines the likelihood that populations can adapt to stress conditions. Generally, the reduction in the population size that accompanies abrupt environmental changes makes it difficult to generate and select adaptive mutations. However, in systems with high genetic diversity, as happens in RNA viruses, mutations with beneficial effects under new conditions can already be present in the population, facilitating adaptation. In this work, we have propagated an RNA bacteriophage (Qβ) at temperatures higher than the optimum, following different patterns of change. We have determined the fitness values and the consensus sequences of all lineages throughout the evolutionary process in order to establish correspondences between fitness variations and adaptive pathways. Our results show that populations subjected to a sudden temperature change gain fitness and fix mutations faster than those subjected to gradual changes, differing also in the particular selected mutations. The life-history of populations prior to the environmental change has great importance in the dynamics of adaptation. The conclusion is that in the bacteriophage Qβ, the standing genetic diversity together with the rate of temperature change determine both the rapidity of adaptation and the followed evolutionary pathways.

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