scholarly journals Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015-17

2020 ◽  
Author(s):  
Everlyn Kamau ◽  
James R. Otieno ◽  
Nickson Murunga ◽  
John W. Oketch ◽  
Joyce M. Ngoi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Evolutionary Dynamics ◽  
Fusion Gene ◽  
Geographical Area ◽  
Strong Support ◽  
Antigenic Site ◽  
Viral Population ◽  
Synonymous Change ◽  
Syncytial Virus ◽  
Group B

AbstractRespiratory syncytial virus (RSV) circulates worldwide and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in 9 health facilities across a defined geographical area (890 km2), over 2 RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple viral introductions into the area and co-circulation of distinct genetic groups or clusters, which transmitted and diversified locally but with varying frequency. Bayesian analyses indicated a strong spatially and temporally structured viral population suggesting extensive within-epidemic virus transmission. Phylogeographic analysis provided a strong support for epidemiological linkage from one central health facility to other facilities. Increase in relative diversity paralleled increase in seasonal viral incidence. Importantly, we identified a cluster of viruses (n=91) that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel non-synonymous change (K68Q) in antigenic site Ø in the Fusion gene. A different non-synonymous change K68N was recently associated with escape from a potent neutralizing monoclonal antibody (MEDI8897). RSVB diversity was additionally marked by signature non-synonymous substitutions that were unique to particular genomic clusters, some of which were under diversifying selection. Our findings provide insights into recent evolutionary and epidemiologic behaviors of RSV group B, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic development strategies.

scholarly journals Genomic epidemiology and evolutionary dynamics of respiratory syncytial virus group B in Kilifi, Kenya, 2015–17

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Everlyn Kamau ◽  
James R Otieno ◽  
Nickson Murunga ◽  
John W Oketch ◽  
Joyce M Ngoi ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Evolutionary Dynamics ◽  
Geographical Area ◽  
Antigenic Site ◽  
Respiratory Illness ◽  
Antigenic Variant ◽  
Genomic Epidemiology ◽  
Multiple Virus ◽  
Syncytial Virus ◽  
Group B

Abstract Respiratory syncytial virus (RSV) circulates worldwide, occurring seasonally in communities, and is a leading cause of acute respiratory illness in young children. There is paucity of genomic data from purposively sampled populations by which to investigate evolutionary dynamics and transmission patterns of RSV. Here we present an analysis of 295 RSV group B (RSVB) genomes from Kilifi, coastal Kenya, sampled from individuals seeking outpatient care in nine health facilities across a defined geographical area (∼890 km2), over two RSV epidemics between 2015 and 2017. RSVB diversity was characterized by multiple virus introductions into the area and co-circulation of distinct genetic clusters, which transmitted and diversified locally with varying frequency. Increase in relative genetic diversity paralleled seasonal virus incidence. Importantly, we identified a cluster of viruses that emerged in the 2016/17 epidemic, carrying distinct amino-acid signatures including a novel nonsynonymous change (K68Q) in antigenic site ∅ in the Fusion protein. RSVB diversity was additionally marked by signature nonsynonymous substitutions that were unique to particular genomic clusters, some under diversifying selection. Our findings provide insights into recent evolutionary and epidemiological behaviors of RSVB, and highlight possible emergence of a novel antigenic variant, which has implications on current prophylactic strategies in development.

scholarly journals Molecular Evolution of Respiratory Syncytial Virus Fusion Gene, Canada, 2006–2010

2012 ◽  
Vol 18 (1) ◽  
pp. 120-124 ◽  
Author(s):  
Jesse Papenburg ◽  
Julie Carbonneau ◽  
Marie-Ève Hamelin ◽  
Sandra Isabel ◽  
Xavier Bouhy ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Molecular Evolution ◽  
Fusion Gene ◽  
Virus Fusion ◽  
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 Clinical patterns and seasonal trends in respiratory syncytial virus hospitalizations in São Paulo, Brazil

2001 ◽  
Vol 43 (3) ◽  
pp. 125-131 ◽  
Author(s):  
Sandra E. VIEIRA ◽  
Klaus E. STEWIEN ◽  
Divina A. O. QUEIROZ ◽  
Edison L. DURIGON ◽  
Thomas J. TÖRÖK ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lower Respiratory Tract ◽  
Respiratory Diseases ◽  
Respiratory Viruses ◽  
Hospitalized Children ◽  
Seasonal Trends ◽  
Group A ◽  
Clinical Patterns ◽  
Syncytial Virus ◽  
Group B

The respiratory viruses are recognized as the most frequent lower respiratory tract pathogens for infants and young children in developed countries but less is known for developing populations. The authors conducted a prospective study to evaluate the occurrence, clinical patterns, and seasonal trends of viral infections among hospitalized children with lower respiratory tract disease (Group A). The presence of respiratory viruses in children's nasopharyngeal was assessed at admission in a pediatric ward. Cell cultures and immunofluorescence assays were used for viral identification. Complementary tests included blood and pleural cultures conducted for bacterial investigation. Clinical data and radiological exams were recorded at admission and throughout the hospitalization period. To better evaluate the results, a non- respiratory group of patients (Group B) was also constituted for comparison. Starting in February 1995, during a period of 18 months, 414 children were included- 239 in Group A and 175 in Group B. In Group A, 111 children (46.4%) had 114 viruses detected while only 5 children (2.9%) presented viruses in Group B. Respiratory Syncytial Virus was detected in 100 children from Group A (41.8%), Adenovirus in 11 (4.6%), Influenza A virus in 2 (0.8%), and Parainfluenza virus in one child (0.4%). In Group A, aerobic bacteria were found in 14 cases (5.8%). Respiratory Syncytial Virus was associated to other viruses and/or bacteria in six cases. There were two seasonal trends for Respiratory Syncytial Virus cases, which peaked in May and June. All children affected by the virus were younger than 3 years of age, mostly less than one year old. Episodic diffuse bronchial commitment and/or focal alveolar condensation were the clinical patterns more often associated to Respiratory Syncytial Virus cases. All children from Group A survived. In conclusion, it was observed that Respiratory Syncytial Virus was the most frequent pathogen found in hospitalized children admitted for severe respiratory diseases. Affected children were predominantly infants and boys presenting bronchiolitis and focal pneumonias. Similarly to what occurs in other subtropical regions, the virus outbreaks peak in the fall and their occurrence extends to the winter, which parallels an increase in hospital admissions due to respiratory diseases.

The Design of Vaccines Based on the Shielding of Antigenic Site Ø of a Respiratory Syncytial Virus Fusion Protein Immunogen

2020 ◽  
pp. 2000714
Author(s):  
Steven J. Frey ◽  
Chad Varner ◽  
Ammar Arsiwala ◽  
Michael G. Currier ◽  
Martin L. Moore ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Fusion Protein ◽  
Antigenic Site ◽  
Virus Fusion ◽  
Syncytial Virus

scholarly journals Trivalency of a Nanobody Specific for the Human Respiratory Syncytial Virus Fusion Glycoprotein Drastically Enhances Virus Neutralization and Impacts Escape Mutant Selection

2016 ◽  
Vol 60 (11) ◽  
pp. 6498-6509 ◽  
Author(s):  
Concepción Palomo ◽  
Vicente Mas ◽  
Laurent Detalle ◽  
Erik Depla ◽  
Olga Cano ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Antigenic Site ◽  
Serial Passage ◽  
Human Respiratory Syncytial Virus ◽  
Escape Mutant ◽  
Comprehensive Description ◽  
Mutant Selection ◽  
Fusion Glycoprotein ◽  
Escape Mutants ◽  
Syncytial Virus

ABSTRACTALX-0171 is a trivalent Nanobody derived from monovalent Nb017 that binds to antigenic site II of the human respiratory syncytial virus (hRSV) fusion (F) glycoprotein. ALX-0171 is about 6,000 to 10,000 times more potent than Nb017 in neutralization tests with strains of hRSV antigenic groups A and B. To explore the effect of this enhanced neutralization on escape mutant selection, viruses resistant to either ALX-0171 or Nb017 were isolated after serial passage of the hRSV Long strain in the presence of suboptimal concentrations of the respective Nanobodies. Resistant viruses emerged notably faster with Nb017 than with ALX-0171 and in both cases contained amino acid changes in antigenic site II of hRSV F. Detailed binding and neutralization analyses of these escape mutants as well as previously described mutants resistant to certain monoclonal antibodies (MAbs) offered a comprehensive description of site II mutations which are relevant for neutralization by MAbs and Nanobodies. Notably, ALX-0171 showed a sizeable neutralization potency with most escape mutants, even with some of those selected with the Nanobody, and these findings make ALX-0171 an attractive antiviral for treatment of hRSV infections.

scholarly journals Evolution of respiratory syncytial virus genotype BA in Kilifi, Kenya, 15 years on

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Everlyn Kamau ◽  
James R. Otieno ◽  
Clement S. Lewa ◽  
Anthony Mwema ◽  
Nickson Murunga ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Population ◽  
Seasonal Fluctuations ◽  
Surveillance Period ◽  
Virus Genotype ◽  
Discrete Location ◽  
Glycoprotein Gene ◽  
Syncytial Virus ◽  
Group B ◽  
Vulnerable Adults

AbstractRespiratory syncytial virus (RSV) is recognised as a leading cause of severe acute respiratory disease and deaths among infants and vulnerable adults. Clinical RSV isolates can be divided into several known genotypes. RSV genotype BA, characterised by a 60-nucleotide duplication in the G glycoprotein gene, emerged in 1999 and quickly disseminated globally replacing other RSV group B genotypes. Continual molecular epidemiology is critical to understand the evolutionary processes maintaining the success of the BA viruses. We analysed 735 G gene sequences from samples collected from paediatric patients in Kilifi, Kenya, between 2003 and 2017. The virus population comprised of several genetically distinct variants (n = 56) co-circulating within and between epidemics. In addition, there was consistent seasonal fluctuations in relative genetic diversity. Amino acid changes increasingly accumulated over the surveillance period including two residues (N178S and Q180R) that mapped to monoclonal antibody 2D10 epitopes, as well as addition of putative N-glycosylation sequons. Further, switching and toggling of amino acids within and between epidemics was observed. On a global phylogeny, the BA viruses from different countries form geographically isolated clusters suggesting substantial localized variants. This study offers insights into longitudinal population dynamics of a globally endemic RSV genotype within a discrete location.

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