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

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.

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Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models

Mathematical Biosciences ◽

10.1016/j.mbs.2006.08.018 ◽

2007 ◽

Vol 209 (1) ◽

pp. 222-239 ◽

Cited By ~ 57

Author(s):

L.J. White ◽

J.N. Mandl ◽

M.G.M. Gomes ◽

A.T. Bodley-Tickell ◽

P.A. Cane ◽

...

Keyword(s):

Time Series ◽

Respiratory Syncytial Virus ◽

Transmission Dynamics ◽

Multiple Time ◽

Multiple Time Series ◽

Nested Models ◽

Syncytial Virus

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Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A) Despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus Evolution?

Journal of Virology ◽

10.1128/jvi.00467-15 ◽

2015 ◽

Vol 89 (15) ◽

pp. 7776-7785 ◽

Cited By ~ 39

Author(s):

Alfonsina Trento ◽

Leyda Ábrego ◽

Rosa Rodriguez-Fernandez ◽

Maria Isabel González-Sánchez ◽

Felipe González-Martínez ◽

...

Keyword(s):

Genetic Diversity ◽

Respiratory Syncytial Virus ◽

Positive Selection ◽

G Protein ◽

Human Respiratory Syncytial Virus ◽

Antigenic Drift ◽

Clear Correlation ◽

Published Data ◽

Group A ◽

Syncytial Virus

ABSTRACTWorldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV) group A sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. Multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the GA2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in Spain and Panama. Reactivity of group A viruses with monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G glycoprotein failed to correlate genotype diversification with antibody reactivity. Additionally, no clear correlation was found between changes in strain-variable epitopes and predicted sites of positive selection, despite both traits being associated with the C-terminal third of the G glycoprotein. Hence, our data do not lend support to the proposed antibody-driven selection of variants as a major determinant of hRSV evolution. Other alternative mechanisms are considered to account for the high degree of hRSV G-protein variability.IMPORTANCEAn unusual characteristic of the G glycoprotein of human respiratory syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher rates than synonymous (S) changes, reaching dN/dS values at certain sites predictive of positive selection. Since these sites cluster preferentially in the C-terminal third of the G protein, like certain epitopes recognized by murine antibodies, it was proposed that immune (antibody) selection might be driving the apparent positive selection, analogous to the antigenic drift observed in the influenza virus hemagglutinin (HA). However, careful antigenic and genetic comparison of the G glycoprotein does not provide evidence of antigenic drift in the G molecule, in agreement with recently published data which did not indicate antigenic drift in the G protein with human sera. Alternative explanations to the immune-driven selection hypothesis are offered to account for the high level of G-protein genetic diversity highlighted in this study.

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Genetic Diversity of the Host and Severe Respiratory Syncytial Virus-Induced Lower Respiratory Tract Infection

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0b013e31818c8d17 ◽

2009 ◽

Vol 28 (2) ◽

pp. 135-140 ◽

Cited By ~ 19

Author(s):

Virginia Amanatidou ◽

Stavros Apostolakis ◽

Demetrios A. Spandidos

Keyword(s):

Genetic Diversity ◽

Respiratory Syncytial Virus ◽

Tract Infection ◽

Respiratory Tract ◽

Respiratory Tract Infection ◽

Lower Respiratory Tract Infection ◽

Lower Respiratory Tract ◽

Severe Respiratory Syncytial Virus ◽

Syncytial Virus

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Cohort profile: A Prospective Household cohort study of Influenza, Respiratory syncytial virus and other respiratory pathogens community burden and Transmission dynamics in South Africa, 2016–2018

Influenza and Other Respiratory Viruses ◽

10.1111/irv.12881 ◽

2021 ◽

Author(s):

Cheryl Cohen ◽

Meredith L. McMorrow ◽

Neil A. Martinson ◽

Kathleen Kahn ◽

Florette K. Treurnicht ◽

...

Keyword(s):

South Africa ◽

Cohort Study ◽

Respiratory Syncytial Virus ◽

Transmission Dynamics ◽

Respiratory Pathogens ◽

Syncytial Virus

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Seasonality, molecular epidemiology, and virulence of Respiratory Syncytial Virus (RSV): A perspective into the Brazilian Influenza Surveillance Program

PLoS ONE ◽

10.1371/journal.pone.0251361 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251361

Author(s):

Lucas A. Vianna ◽

Marilda M. Siqueira ◽

Lays P. B. Volpini ◽

Iuri D. Louro ◽

Paola C. Resende

Keyword(s):

Genetic Diversity ◽

Viral Load ◽

Respiratory Syncytial Virus ◽

Disease Severity ◽

Clinical Severity ◽

Influenza Surveillance ◽

Surveillance Program ◽

Inverse Association ◽

Severe Acute Respiratory Infection ◽

Syncytial Virus

Background Respiratory Syncytial Virus (RSV) is the main cause of pediatric morbidity and mortality. The complex evolution of RSV creates a need for worldwide surveillance, which may assist in the understanding of multiple viral aspects. Objectives This study aimed to investigate RSV features under the Brazilian Influenza Surveillance Program, evaluating the role of viral load and genetic diversity in disease severity and the influence of climatic factors in viral seasonality. Methodology We have investigated the prevalence of RSV in children up to 3 years of age with severe acute respiratory infection (SARI) in the state of Espirito Santo (ES), Brazil, from 2016 to 2018. RT-qPCR allowed for viral detection and viral load quantification, to evaluate association with clinical features and mapping of local viral seasonality. Gene G sequencing and phylogenetic reconstruction demonstrated local genetic diversity. Results Of 632 evaluated cases, 56% were caused by RSV, with both subtypes A and B co-circulating throughout the years. A discrete inverse association between average temperature and viral circulation was observed. No correlation between viral load and disease severity was observed, but children infected with RSV-A presented a higher clinical severity score (CSS), stayed longer in the hospital, and required intensive care, and ventilatory support more frequently than those infected by RSV-B. Regarding RSV diversity, some local genetic groups were observed within the main genotypes circulation RSV-A ON1 and RSV-B BA, with strains showing modifications in the G gene amino acid chain. Conclusion Local RSV studies using the Brazilian Influenza Surveillance Program are relevant as they can bring useful information to the global RSV surveillance. Understanding seasonality, virulence, and genetic diversity can aid in the development and suitability of antiviral drugs, vaccines, and assist in the administration of prophylactic strategies.

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