scholarly journals Stabilizing selection of seasonal influenza receptor binding in populations with partial immunity

2020 ◽  
Author(s):  
James A. Hay ◽  
Alvin Junus ◽  
Steven Riley ◽  
Hsiang-Yu Yuan
Keyword(s):  
Phylogenetic Analysis ◽  
Receptor Binding ◽  
Seasonal Influenza ◽  
Immune Escape ◽  
Stabilizing Selection ◽  
Human Influenza ◽  
Net Charge ◽  
Binding Avidity ◽  
Selection Of ◽  
Partial Immunity

AbstractMutations that alter cellular receptor binding of influenza hemagglutinin (HA) have profound effects on immune escape. Despite its high mutation rate, it is not fully understood why human influenza HA displays limited antigenic diversity across circulating viruses. We applied phylogenetic analysis and phylodynamic modeling to understand the evolutionary and epidemiological effects of binding avidity adaptation in humans using net charge as a marker for receptor binding avidity. Using 686 human influenza A/H3N2 HA sequences, we found that HA net charge followed an age-specific pattern. Phylogenetic analysis suggested that many binding variants have reduced fitness. Next, we developed an individual-based disease dynamic model embedded with within-host receptor binding adaptation and immune escape in a population with varied partial immunity. The model showed that mean binding avidity was unable to adapt to values that maximized transmissibility due to competing selective forces between within- and between-host levels. Overall, we demonstrated stabilizing selection of virus binding in a population with increasing partial immunity. These findings have potential implications in understanding the evolutionary mechanisms that determine the intensity of seasonal influenza epidemics.

scholarly journals Selection of Receptor-Binding Variants of Human Influenza A and B Viruses in Baby Hamster Kidney Cells

Virology ◽  
1999 ◽  
Vol 262 (1) ◽  
pp. 31-38 ◽  
Author(s):  
E.A. Govorkova ◽  
M.N. Matrosovich ◽  
A.B. Tuzikov ◽  
N.V. Bovin ◽  
C. Gerdil ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Influenza A ◽  
Kidney Cells ◽  
Baby Hamster Kidney ◽  
Human Influenza ◽  
Selection Of ◽  
Baby Hamster Kidney Cells

scholarly journals Receptor binding, immune escape, and protein stability direct the natural selection of SARS-CoV-2 variants

2021 ◽  
Vol 297 (4) ◽  
pp. 101208
Author(s):  
Vaibhav Upadhyay ◽  
Alexandra Lucas ◽  
Sudipta Panja ◽  
Ryuki Miyauchi ◽  
Krishna M.G. Mallela
Keyword(s):  
Natural Selection ◽  
Protein Stability ◽  
Receptor Binding ◽  
Immune Escape ◽  
Selection Of

scholarly journals Molecular and phylogenetic analysis reveals new diversity of Dunaliella salina from hypersaline environments

2021 ◽  
pp. 1-11
Author(s):  
Andrea Highfield ◽  
Angela Ward ◽  
Richard Pipe ◽  
Declan C. Schroeder
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analysis ◽  
Dunaliella Salina ◽  
Phylogenetic Analyses ◽  
Ssu Rdna ◽  
Lsu Rdna ◽  
Hypersaline Environments ◽  
Rdna Its ◽  
Β Carotene ◽  
Selection Of

Abstract Twelve hyper-β carotene-producing strains of algae assigned to the genus Dunaliella salina have been isolated from various hypersaline environments in Israel, South Africa, Namibia and Spain. Intron-sizing of the SSU rDNA and phylogenetic analysis of these isolates were undertaken using four commonly employed markers for genotyping, LSU rDNA, ITS, rbcL and tufA and their application to the study of Dunaliella evaluated. Novel isolates have been identified and phylogenetic analyses have shown the need for clarification on the taxonomy of Dunaliella salina. We propose the division of D. salina into four sub-clades as defined by a robust phylogeny based on the concatenation of four genes. This study further demonstrates the considerable genetic diversity within D. salina and the potential of genetic analyses for aiding in the selection of prospective economically important strains.

scholarly journals Rapid Evolution of SARS-CoV-2 Challenges Human Defenses

2021 ◽  
Author(s):  
Carlos M. Duarte ◽  
David Ketcheson ◽  
Víctor M. Eguíluz ◽  
Susana Agustí ◽  
Juan Fernández-Gracia ◽  
...  
Keyword(s):  
Big Data ◽  
Receptor Binding ◽  
Evolutionary Ecology ◽  
Rapid Evolution ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Future Behavior ◽  
Human Infections ◽  
Selection Of

AbstractEvolutionary ecology theory provides an avenue to anticipate the future behavior of SARS-CoV-2. Here we quantify the accelerating evolution of SARS-CoV-2 by tracking the SARS-CoV-2 mutation globally, with a focus on the Receptor Binding Domain (RBD) of the spike protein believed to determine infectivity. We estimate that 384 million people were infected by March 1st, 2021, producing up to 1021 copies of the virus, with one new RBD variant appearing for every 600,000 human infections, resulting in approximately three new effective RBD variants produced daily. Doubling the number of RBD variants every 71.67 days followed by selection of the most infective variants challenges our defenses and calls for a shift to anticipatory, rather than reactive tactics.One-Sentence SummaryAccelerating evolution of SARS-CoV-2 demands formulating universal vaccines and treatments based on big-data simulations of possible new variants.

Phylogenetic analysis of DNA sequence data.

2021 ◽  
pp. 265-282
Author(s):  
Sergei A. Subbotin
Keyword(s):  
Phylogenetic Analysis ◽  
Sequence Data ◽  
Sequence Similarity ◽  
Phylogenetic Study ◽  
Public Database ◽  
Sample Collection ◽  
Minimum Evolution ◽  
Molecular Phylogenetic ◽  
Pcr Products ◽  
Selection Of

Abstract The goal of phylogenetics is to construct relationships that are true representations of the evolutionary history of a group of organisms or genes. The history inferred from phylogenetic analysis is usually depicted as branching in tree-like diagrams or networks. In nematology, phylogenetic studies have been applied to resolve a wide range of questions dealing with improving classifications and testing evolution processes, such as co-evolution, biogeography and many others. There are several main steps involved in a phylogenetic study: (i) selection of ingroup and outgroup taxa for a study; (ii) selection of one or several gene fragments for a study; (iii) sample collection, obtaining PCR products and sequencing of gene fragments; (iv) visualization, editing raw sequence data and sequence assembling; (v) search for sequence similarity in a public database; (vi) making and editing multiple alignment of sequences; (vii) selecting appropriate DNA model for a dataset; (viii) phylogenetic reconstruction using minimum evolution, maximum parsimony, maximum likelihood and Bayesian inference; (ix) visualization of tree files and preparation of tree for a publication; and (x) sequence submission to a public database. Molecular phylogenetic study requires particularly careful planning because it is usually relatively expensive in terms of the cost in reagents and time.

scholarly journals Quantitative genetic variability maintained by mutation-stabilizing selection balance: sampling variation and response to subsequent directional selection

1989 ◽  
Vol 54 (1) ◽  
pp. 45-58 ◽  
Author(s):  
Peter D. Keightley ◽  
William G. Hill
Keyword(s):  
Genetic Variance ◽  
Directional Selection ◽  
Quantitative Character ◽  
Stabilizing Selection ◽  
Effective Population ◽  
Selection Responses ◽  
Quantitative Genetic ◽  
Before And After ◽  
Cage Population ◽  
Selection Of

SummaryA model of genetic variation of a quantitative character subject to the simultaneous effects of mutation, selection and drift is investigated. Predictions are obtained for the variance of the genetic variance among independent lines at equilibrium with stabilizing selection. These indicate that the coefficient of variation of the genetic variance among lines is relatively insensitive to the strength of stabilizing selection on the character. The effects on the genetic variance of a change of mode of selection from stabilizing to directional selection are investigated. This is intended to model directional selection of a character in a sample of individuals from a natural or long-established cage population. The pattern of change of variance from directional selection is strongly influenced by the strengths of selection at individual loci in relation to effective population size before and after the change of regime. Patterns of change of variance and selection responses from Monte Carlo simulation are compared to selection responses observed in experiments. These indicate that changes in variance with directional selection are not very different from those due to drift alone in the experiments, and do not necessarily give information on the presence of stabilizing selection or its strength.

scholarly journals Antivirals for treatment and prevention of human seasonal influenza

2006 ◽  
Vol 27 (4) ◽  
pp. 163
Author(s):  
Clayton Chiu ◽  
Robert Booy ◽  
Dominic E Dwyer
Keyword(s):  
Public Health ◽  
At Risk ◽  
Seasonal Influenza ◽  
Human Influenza ◽  
Public Health Strategy ◽  
Risk Population ◽  
Population Groups ◽  
Treatment And Prevention ◽  
Health Strategy ◽  
Seasonal Epidemic

While immunisation is the primary public health strategy for prevention of influenza, antivirals are important complementary measures for controlling seasonal/epidemic human influenza, especially when there is a mismatch between circulating and vaccine strains and in at-risk population groups.

scholarly journals Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness and Decrease Pandemic Potential

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Pengxiang Chang ◽  
Joshua E. Sealy ◽  
Jean-Remy Sadeyen ◽  
Sushant Bhat ◽  
Deimante Lukosaityte ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Avian Influenza ◽  
Virus Replication ◽  
Receptor Binding ◽  
Immune Escape ◽  
Influenza Viruses ◽  
Escape Mutant ◽  
Hemagglutinin Protein ◽  
Ha Protein ◽  
The Impact

ABSTRACT H7N9 avian influenza viruses (AIVs) continue to evolve and remain a huge threat to human health and the poultry industry. Previously, serially passaging the H7N9 A/Anhui/1/2013 virus in the presence of homologous ferret antiserum resulted in immune escape viruses containing amino acid substitutions alanine to threonine at residues 125 (A125T) and 151 (A151T) and leucine to glutamine at residue 217 (L217Q) in the hemagglutinin (HA) protein. These HA mutations have also been found in field isolates in 2019. To investigate the potential threat of serum escape mutant viruses to humans and poultry, the impact of these HA substitutions, either individually or in combination, on receptor binding, pH of fusion, thermal stability, and virus replication were investigated. Our results showed the serum escape mutant formed large plaques in Madin-Darby canine kidney (MDCK) cells and grew robustly in vitro and in ovo. They had a lower pH of fusion and increased thermal stability. Of note, the serum escape mutant completely lost the ability to bind to human-like receptor analogues. Further analysis revealed that N-linked glycosylation, as a result of A125T or A151T substitutions in HA, resulted in reduced receptor-binding avidity toward both human and avian-like receptor analogues, and the A125T+A151T mutations completely abolished human-like receptor binding. The L217Q mutation enhanced the H7N9 acid and thermal stability while the A151T mutation dramatically decreased H7N9 HA thermal stability. To conclude, H7N9 AIVs that contain A125T+A151T+L217Q mutations in the HA protein may pose a reduced pandemic risk but remain a heightened threat for poultry. IMPORTANCE Avian influenza H7N9 viruses have been causing disease outbreaks in poultry and humans. We previously determined that propagation of H7N9 virus in virus-specific antiserum gives rise to mutant viruses carrying mutations A125T+A151T+L217Q in their hemagglutinin protein, enabling the virus to overcome vaccine-induced immunity. As predicted, these immune escape mutations were also observed in the field viruses that likely emerged in the immunized or naturally exposed birds. This study demonstrates that the immune escape mutants also (i) gained greater replication ability in cultured cells and in chicken embryos as well as (ii) increased acid and thermal stability but (iii) lost preferences for binding to human-type receptor while maintaining binding for the avian-like receptor. Therefore, they potentially pose reduced pandemic risk. However, the emergent virus variants containing the indicated mutations remain a significant risk to poultry due to antigenic drift and improved fitness for poultry.

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