English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

To the Editor—Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections such as bronchiolitis and pneumonia in infants and young children [1]. The virus can be classified into 2 subgroups, A and B, and further divided into genotypes based on the genetic sequence of the G gene. In 2012, a novel genotype known as ON1, which is characterized by a 72-nucleotide duplication in its G gene, was reported [2]. The ON1 virus has prevailed in many parts of the world, becoming the predominant genotype of the virus [3]. It remains unknown how the genotype was first generated and how it has come to dominate. A recent report in The Journal of Infectious Diseases by Comas-García et al suggested that there were multiple duplication events leading to at least 3 independent emergences of the ON1 virus from its ancestral genotype, GA2 [4]. This conclusion was based on an amino-acid sequence motif, in particular, amino-acid positions 273 and 274 in the G gene. Here, we describe the amino-acid sequence motif at these positions as “XX” for the GA2 genotype and “XXXX” for the ON1 genotype; the sites were duplicated in the ON1. ComasGarcía et al found 4 patterns among the GA2 viruses (NL, NP, YP, and YL) and 3 patterns among the ON1 viruses (NPNP, YPYP, and YLYL). Based on these findings, they suggested that 3 independent events led to the emergence of the ON1 genotype: from NP to NPNP, from YP to YPYP, and from YL to YLYL. In our phylogenetic analysis, a tree was constructed using only amino-acid sequences in the duplicated region including the motif (a total of 23 sites; Figure 1, left panel), and the results initially supported this theory. However, the analysis raised a concern. The length of the sequence is too short to deduce the evolutionary pathway of the virus. Actually, YPYP and YLYL viruses cluster into a monophyletic group in the phylogenetic tree constructed by ComasGarcía et al [4]. Although they did not describe the phylogenetic model they used, we also confirmed that the YPYP and YLYL viruses shared a common ancestor after divergence from the YL viruses (the GA2 genotype) based on a maximum-likelihood tree created using not only the short amino-acid motif but also the nucleotide sequence of the entire G gene (Figure 1, right panel). The same tree topology was confirmed using other phylogenetic models, including a neighbor-joining tree and an UPGMA tree (data not shown). Based on these results, it is more likely that the ON1 genotype was generated as a result of a single duplication event. Thereafter, the polymorphism YPYP/YLYL was generated. It is still intriguing to see that the polymorphism YP/YL was retained both before and after the duplication event. The site could be under positive selection pressure. It should be noted that the NPNP virus (RSVA/Homo sapiens/JOR/A0215/2011) was generated from NP viruses by an independent duplication event, which can be clearly distinguished from the duplication event leading to the emergence of YPYP and YLYL viruses. Although the NPNP virus possesses the same duplication site, we suggest that it should not be classified as the ON1 but as the GA2 genotype. We agree that the 72-nucleotide duplication site is a characteristic feature of the ON1 virus; however, the presence of the duplication site is not definitive of the genotype. Each genotype encompasses a group of individual viruses within a close genetic distance; the NPNP virus does not have the ON1 genotype, given its close distance to NL, NP, YP, and YL viruses (all have the GA2 genotype) and a clear distinction from YPYP and YLYL viruses (Figure 1, right panel). Although we do not agree with the theory that there were multiple duplication events leading to 3 independent emergences of the ON1 genotype, importance to elucidate the mechanismsunderlying how and why the duplicationoccurred in the G gene will notdecrease. In addition to the duplication event that resulted in the emergence of the ON1 genotype, the NPNP virus was generated by an independent duplication event. The duplication of a part of the G gene has also been reported in the RSV subgroup B and in other members of the Paramyxoviridae family (eg, human metapneumovirus) [5–7]. Further study is needed to elucidate the evolutionary, virological, and clinical significance of this duplication.

Multiple or Single Duplication Events Leading to the Emergence of a Novel Genotype of Respiratory Syncytial Virus