Rapid Spread and Diversification of Respiratory Syncytial Virus Genotype ON1, Kenya - Volume 20, Number 6—June 2014 - Emerging Infectious Disease journal - CDC

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Rapid Spread and Diversification of Respiratory Syncytial Virus Genotype ON1, Kenya - Volume 20, Number 6—June 2014 - Emerging Infectious Disease journal - CDC

Volume 20, Number 6—June 2014

Research

Rapid Spread and Diversification of Respiratory Syncytial Virus Genotype ON1, Kenya

Article Contents

• Materials and Methods
• Results
• Discussion
• Acknowledgments
• References
• Figure 1
• Figure 2
• Figure 3
• Figure 4
• Figure 5
• Table 1
• Table 2
• Technical Appendix - 631 KB 
• Suggested Citation

Charles N. Agoti , James R. Otieno, Caroline W. Gitahi, Patricia A. Cane, and D. James Nokes

Author affiliations: Kenya Medical Research Institute–Wellcome Trust Research Programme, Kilifi, Kenya (C.N. Agoti, J.R. Otieno, C.W. Gitahi, D.J. Nokes); Public Health England, London, UK (P.A. Cane); University of Warwick and WIDER, Coventry, UK (D.J. Nokes)

Suggested citation for this article

Abstract

Respiratory syncytial virus genotype ON1, which is characterized by a 72-nt duplication in the attachment protein gene, has been detected in >10 countries since first identified in Ontario, Canada, in 2010. We describe 2 waves of genotype ON1 infections among children admitted to a rural hospital in Kenya during 2012. Phylogenetic analysis of attachment protein gene sequences showed multiple introductions of genotype ON1; variants distinct from the original Canadian viruses predominated in both infection waves. The genotype ON1 dominated over the other group A genotypes during the second wave, and some first wave ON1 variants reappeared in the second wave. An analysis of global genotype ON1 sequences determined that this genotype has become considerably diversified and has acquired signature coding mutations within immunogenic regions, and its most recent common ancestor dates to ≈2008–2009. Surveillance of genotype ON1 contributes to an understanding of the mechanisms of rapid emergence of respiratory viruses.

Human respiratory syncytial virus (RSV) is the major viral cause of bronchiolitis and pneumonia in infants and also a major cause of severe respiratory illness in the elderly (1). RSV infection usually occurs in annual epidemics, and the virus can re-infect persons throughout life. RSV isolates fall into 2 groups, A and B, and each group includes multiple genotypes. RSV epidemics are often caused by several variants of >1 RSV genotypes, and the dominant genotype is usually replaced each year (2). RSV’s most variable protein, the attachment (G) glycoprotein, is also a target of protective antibody responses, and analysis of its encoding genome portion shows continuous accumulation of genetic changes leading to antigenic drift (3,4). However, as a nonsegmented, single-stranded RNA virus, RSV does not show the abrupt antigenic changes that are sometimes seen in influenza A viruses. The abrupt changes in influenza A viruses commonly arise when genome segments reassort, sometimes acquiring new surface protein genes from animal sources, leading to antigenic shift as was seen in the recent influenza A(H1N1) pandemic strain (5). Nevertheless, twice in recent years, a distinct new genotype of RSV has arisen as a result of duplication within the G gene. The first of these new genotypes was detected in 1999 when 3 group B viruses with a 60-nt duplication in the C-terminal region of the G gene, which encodes strain-specific epitopes (4), were isolated in Buenos Aires, Argentina (6). This genotype was also observed in a retrospective analysis of RSV samples from 1998 to 1999 in Madrid, Spain (7). This novel genotype spread rapidly and by 2003 was being detected around the world; by 2006, it had become the predominant group B genotype (7,8).

In December 2010, a novel RSV group A genotype, ON1, with a 72-nt duplication in the C-terminal region of the G gene, was detected in Ontario, Canada (9). This genotype was also detected in Malaysia, India, and South Korea at the end of 2011 (10–12) and in Germany, Italy, South Africa, Japan, China, and Kenya in 2012 (13–15) (GenBank, unpub. data). The emergence and spread of these new genotypes, which can be readily tracked by G gene sequencing, provide an opportunity to re-examine 1) the interconnectedness of RSV epidemics at various levels (e.g., global, country, and community levels), 2) the spatial–temporal scale of the spread of variants, and 3) the pace and nature of associated genetic changes. Such examinations have the potential to bring new insights regarding how RSV persists to cause recurrent epidemics in human populations.

We conducted a detailed analysis of G gene variability of the ON1 genotype viruses detected among children inpatients at a hospital in rural Kenya in 2012. Two RSV epidemics were observed during the year, and a wave of genotype ON1 cases occurred in each. We compare the phylogenetic relationship between the ON1 viruses detected in Kenya and ON1 viruses worldwide during a similar period.

Acknowledgments

We thank the parents and guardians of children participating in the study. We also thank the clinical and laboratory staff of the Kilifi Viral Epidemiology and Control group who obtained and processed the study specimens. The study is published with permission of director of the Kenya Medical Research Institute.

This work was supported by the Wellcome Trust (grant no. 084633).

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Figures

• Figure 1. A) Number of persons positive for respiratory syncytial virus (RSV) genotype ON1 during 2 infection waves, Kilifi, Kenya, 2012Blue line indicates cases of RSV group A infection; red line...
• Figure 2. Phylogeny of respiratory syncytial virus genotype ON1 viruses detected globally and from Kilifi, KenyaA) Maximum-likelihood, nucleotide-based phylogenetic tree showing the evolutionary relationships of the 77 Kilifi ON1 viruses across...
• Figure 3. A) Geographic locations (indicated by stars) where respiratory syncytial virus genotype ON1 sequences had been detected and reported as of September 8, 2013B) Number of ON1 sequences present in...
• Figure 4. Alignment of unique deduced amino acid sequences from the combined dataset of sequences from the C-terminal third of the attachment protein of respiratory syncytial virus genotype ON1The sequences are...
• Figure 5. Most recent common ancestor analysis of the 65 respiratory syncytial virus genotype ON1 viruses in GenBank and the sequences for ON1 viruses detected in Kilifi, Kenya, during 2012The analysis...

Tables

• Table 1. Occurrence of RSV group A and B viruses and of genotype ON1 in Kilifi, Kenya, 2012
• Table 2. Signature codon changes in circulating global RSV group A genotype ON1 viruses

Technical Appendix

• Technical Appendix. Signature mutations that distinguished the 3 respiratory syncytial virus ON1 lineages identified at Kilifi, Kenya, taxon names, and mean genetic distances between the 3 lineages.  631 KB 

Suggested citation for this article: Agoti CN, Otieno JR, Gitahi CW, Cane PA, Nokes DJ. Rapid spread and diversification of respiratory syncytial virus genotype ON1, Kenya. Emerg Infect Dis. 2014 June [date cited]. http://dx.doi.org/10.3201/eid2006.131438

DOI: 10.3201/eid2006.131438