Distinct patterns of within-host virus populations between two subgroups of human respiratory syncytial virus

Abstract

Human respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young children globally, but little is known about within-host RSV diversity. Here, we characterised within-host RSV populations using deep-sequencing data from 319 nasopharyngeal swabs collected during 2017–2020. RSV-B had lower consensus diversity than RSV-A at the population level, while exhibiting greater within-host diversity. Two RSV-B consensus sequences had an amino acid alteration (K68N) in the fusion (F) protein, which has been associated with reduced susceptibility to nirsevimab (MEDI8897), a novel RSV monoclonal antibody under development. In addition, several minor variants were identified in the antigenic sites of the F protein, one of which may confer resistance to palivizumab, the only licensed RSV monoclonal antibody. The differences in within-host virus populations emphasise the importance of monitoring for vaccine efficacy and may help to explain the different prevalences of monoclonal antibody-escape mutants between the two subgroups.

Temporal dynamics of RSV shedding and genetic diversity in adults during the COVID-19 pandemic in a French hospital, early 2021

“…To ascertain that the consensus sequences we produced did not include mapping errors, raw reads were aligned on the consensus sequence, then the consensus were corrected if needed. We observed that the RSV group A genomes from this study were closely related to those collected during the 2017-2020 period across the United Kingdom, Spain and the Netherlands ( Lin et al, 2021 ), with identity percentages ranging from 99.62% to 99.73%. All the amino acid positions that differed with the RSV group A reference genes are indicated in the Supplementary Figure 2 .…”

RSV Prevention in All Infants: Which Is the Most Preferable Strategy?

“…Polymorphisms in the nirsevimab and palivizumab binding regions have been reported, and although some of these have not been evaluated in neutralization assays, the frequency of isolates with amino acid changes leading to partial resistance is low ( 118 ). Specifically, in a recent analysis of within-host RSV diversity (2017–2020), only 0.8% (2/264) of immunoprophylaxis-naïve participants had RSV-B sequences containing the amino acid change K68N in the F protein, which has been linked to reduced susceptibility to nirsevimab ( 120 ). Despite the potential of neutralization escape mutants, clinical use of palivizumab demonstrated that this has not been a major issue ( 2 ).…”

Antiviral potential of anthraquinones from Polygonaceae, Rubiaceae and Asphodelaceae: Potent candidates in the treatment of SARS-COVID-19, A comprehensive review

“…Human respiratory syncytial virus (RSV) is a negative-sense single-stranded RNA virus ( Lin et al, 2021 ) which is the most frequent cause of infection of the lower part of the respiratory tract. The infection is most common in children under the age group of 5 years, causing mainly bronchiolitis and pneumonia ( Shi et al, 2017 ; Aranda and Polack, 2019 ).…”

“…The compound has been shown to inhibit the virus significantly with an effective concentration (EC 50 ) of 13.06 µmol/L. In addition, emodin has been demonstrated to decrease mRNA expression of cytokine IFN-α ( Lin et al, 2021 ), suggesting that the compound could be developed as an antiviral candidate against human respiratory viral infection. Rhein isolated from the same plant has shown its capability to alleviate infection and injury in lungs caused by the virus in RSV-induced mice.…”