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Review
. 2022 Oct 8:9:20499361221128091.
doi: 10.1177/20499361221128091. eCollection 2022 Jan-Dec.

Clinical and biological consequences of respiratory syncytial virus genetic diversity

Estefany Rios Guzman  1   2 , Judd F Hultquist  3   1   2
Affiliations
Review

Clinical and biological consequences of respiratory syncytial virus genetic diversity

Estefany Rios Guzman et al. Ther Adv Infect Dis. .

Abstract

Respiratory syncytial virus (RSV) is one of the most common etiological agents of global acute respiratory tract infections with a disproportionate burden among infants, individuals over the age of 65, and immunocompromised populations. The two major subtypes of RSV (A and B) co-circulate with a predominance of either group during different epidemic seasons, with frequently emerging genotypes due to RSV's high genetic variability. Global surveillance systems have improved our understanding of seasonality, disease burden, and genomic evolution of RSV through genotyping by sequencing of attachment (G) glycoprotein. However, the integration of these systems into international infrastructures is in its infancy, resulting in a relatively low number (~2200) of publicly available RSV genomes. These limitations in surveillance hinder our ability to contextualize RSV evolution past current canonical attachment glycoprotein (G)-oriented understanding, thus resulting in gaps in understanding of how genetic diversity can play a role in clinical outcome, therapeutic efficacy, and the host immune response. Furthermore, utilizing emerging RSV genotype information from surveillance and testing the impact of viral evolution using molecular techniques allows us to establish causation between the clinical and biological consequences of arising genotypes, which subsequently aids in informed vaccine design and future vaccination strategy. In this review, we aim to discuss the findings from current molecular surveillance efforts and the gaps in knowledge surrounding the consequence of RSV genetic diversity on disease severity, therapeutic efficacy, and RSV-host interactions.

Keywords: clinical outcomes; genetic diversity; genotype; molecular surveillance; respiratory syncytial virus; therapeutic design; whole-genome sequencing.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Representation of molecular surveillance pipeline. Sample collection and preparation of clinical samples from RSV positive populations from global locations in surveillance systems give rise to the ability to track RSV seasonality and rise in emerging genotypes. When performing phylogenetic analysis of the RSV whole-genome sequences, certain circulating genotypes may present differential clinical characteristics, such as clinical severity, transmission, and mortality. These genotypes (depicted in green, purple, and blue) may have varying infectivity, resulting in varying population size with a wide range of treatment efficacy. When observing the molecular underpinnings of each genotype, mutations within RSV open reading frames (ORFs) unique to defined genotypes may influence gene expression, host–pathogen interactions, and immune evasion strategies.
Figure 2.
Figure 2.
Schematic of RSV Virion Structure and Genome. The RSV RNA genome consists of 10 genes of 15.2 kb length that encode 11 proteins. These proteins can be categorized into ribonucleocapsid proteins [phosphoprotein (P), nucleoprotein (N), RNA polymerase (L), M2-1, and M2-2], nonstructural proteins (NS1 and NS2), three surface proteins [small hydrophobic protein (SH) attachment glycoprotein (G), and fusion protein (F)], and matrix protein (M) which surrounds the envelope and nucleocapsid.
Figure 3.
Figure 3.
RSV sequences deposited in National Institute of Health (NIH) sequence database GenBank over time. Plot of the number of publicly available sequences deposited in GenBank from 2000 to 2022. RSV-G sequences are depicted in gray and WGS data are depicted in green.
See this image and copyright information in PMC

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