Immune escaping of the novel genotypes of human respiratory syncytial virus based on gene sequence variation

Abstract

PurposeImmune escaping from host herd immunity has been related to changes in viral genomic sequences. The study aimed to understand the diverse immune responses to different subtypes or genotypes of human respiratory syncytial virus (RSV) in pediatric patients.MethodsThe genomic sequences of different subtypes or RSV genotypes, isolated from Beijing patients, were sequenced and systematically analyzed. Specifically, the antiviral effects of Palivizumab and the cross-reactivity of human sera from RSV-positive patients to different subtypes or genotypes of RSV were determined. Then, the level of 38 cytokines and chemokines in respiratory and serum samples from RSV-positive patients was evaluated.ResultsThe highest nucleotide and amino acid variations and the secondary and tertiary structure diversities among different subtypes or genotypes of RSV were found in G, especially for genotype ON1 with a 72bp-insertion compared to NA1 in subtype A, while more mutations of F protein were found in the NH-2 terminal, including the antigenic site II, the target of Palivizumab, containing one change N276S. Palivizumab inhibited subtype A with higher efficiency than subtype B and had stronger inhibitory effects on the reference strains than on isolated strains. However, RSV-positive sera had stronger inhibitory effects on the strains in the same subtypes or genotypes of RSV. The level of IFN-α2, IL-1α, and IL-1β in respiratory specimens from patients with NA1 was lower than those with ON1, while there were higher TNFα, IFNγ, IL-1α, and IL-1β in the first serum samples from patients with ON1 compared to those with BA9 of subtype B.ConclusionsDiverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.

All Eyes on the Prefusion-Stabilized F Construct, but Are We Missing the Potential of Alternative Targets for Respiratory Syncytial Virus Vaccine Design?

“…Significant differences have been observed between RSV prototype strains and contemporary clinical isolates, including variations in viral replication kinetics, thermal stability, fusion capacity and the nAbs they induce. Therefore, utilizing contemporary isolates ensures a more representative assessment of vaccine efficacy against current circulating viruses [ 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 ]. Moreover, it could be considered highly desirable to include multiple recent isolates of RSV instead of using just one.…”

Sequencing and characterization of human bocavirus genomes from patients diagnosed in Southern France between 2017 and 2022

“…The diversity observed in this study may have an impact on the contagiousness and severity of HBoV1 infections. This could be linked to mutations in the capsid proteins that are involved in attachment of the virus to its host cell, as has been observed for other viruses such as SARS‐CoV‐2 for which mutation in the spike glycoprotein was associated with a high contagiousness 39 or the respiratory syncytial virus for which capacities of immune response were reported to vary according to the viral genotype 40 . Further studies are needed to gain a better knowledge about these points and the impact of given mutations.…”

“…This could be linked to mutations in the capsid proteins that are involved in attachment of the virus to its host cell, as has been observed for other viruses such as SARS-CoV-2 for which mutation in the spike glycoprotein was associated with a high contagiousness 39 or the respiratory syncytial virus for which capacities of immune response were reported to vary according to the viral genotype. 40 Further studies are needed to gain a better knowledge about these points and the impact of given mutations. Intriguingly, stop codons were observed in three genomes from the present study and also in genomes from GenBank at different genome positions.…”

Comparative analysis of human respiratory syncytial virus evolutionary patterns during the COVID-19 pandemic and pre-pandemic periods

“…Neutralizing antibodies targeting the F protein are critical for developing RSV vaccines aiming to prevent infection ( Ruckwardt et al, 2019 ). Recent neutralization assays conducted in China revealed that pediatric patients infected with different subtypes/genotypes of HRSV exhibited varying antibody titers against different subtypes/genotypes of HRSV ( Zhou et al, 2023 ). Our study identified amino acids changes at antigenic sites Ø, I, II and VIII within the F protein.…”