Genome-wide study of globally distributed respiratory syncytial virus (RSV) strains implicates diversification utilizing phylodynamics and mutational analysis

Abstract

Respiratory syncytial virus (RSV) is a common respiratory pathogen that causes mild cold-like symptoms and severe lower respiratory tract infections, causing hospitalizations in children, the elderly and immunocompromised individuals. Due to genetic variability, this virus causes life-threatening pneumonia and bronchiolitis in young infants. Thus, we examined 3600 whole genome sequences submitted to GISAID by 31 December 2022 to examine the genetic variability of RSV. While RSVA and RSVB coexist throughout RSV seasons, RSVA is more prevalent, fatal, and epidemic-prone in several countries, including the United States, the United Kingdom, Australia, and China. Additionally, the virus's attachment glycoprotein and fusion protein were highly mutated, with RSVA having higher Shannon entropy than RSVB. The genetic makeup of these viruses contributes significantly to their prevalence and epidemic potential. Several strain-specific SNPs co-occurred with specific haplotypes of RSVA and RSVB, followed by different haplotypes of the viruses. RSVA and RSVB have the highest linkage probability at loci T12844A/T3483C and G13959T/C2198T, respectively. The results indicate that specific haplotypes and SNPs may significantly affect their spread. Overall, this analysis presents a promising strategy for tracking the evolving epidemic situation and genetic variants of RSV, which could aid in developing effective control, prophylactic, and treatment strategies.

Figure 1

A spherical, combined representation of the geographic ranges and evolutionary trees of RSV A and RSV B. The perimeter of the circle is displayed with distinct colors, one for each country, to show the geographical distribution of these two strains.

Figure 2

Both RSVA (A) and RSVB (B) have transmission networks that can be predicted using StrainHub. Direction of transmission is shown by arrows, while nations of origin are denoted by circles of varying colours.

Figure 3

The worldwide spread of 13 more haplotypes of respiratory syncytial virus (RSV) (A) and (RSVB) (B). The size and color of the circles stand in for the total size of the genome and the total number of haplotypes, respectively.

Figure 4

The lollipop plot represents all possible mutations in RSV A (A) and RSV B (B). Each gene is represented by the green bar, and each mutation within that gene is shown on the lollipop as a single-letter change in the coding for an amino acid. Lollipops in blue represent synonymous mutations while those in red represent missense mutations.

Figure 5

Haploview's determination of LDs between SNPs in RSV A (A) and RSV B (A) is shown in the haplotype block. As the association between the LDs grows with colour, from white (the weakest) to crimson (the highest), the colour serves as a reflection of the LDs' true powers. The bases of the genome that have been changed due to mutations are marked in the text at the top of the picture.