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

Xiaohe Zhou; Mingli Jiang; Fengjie Wang; Yuan Qian; Qinwei Song; Yu Sun; Runan Zhu; Fang Wang; Dong Qu; Ling Cao; Lijuan Ma; Yanpeng Xu; Ri De; Linqing Zhao

doi:10.3389/fimmu.2022.1084139

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

Front Immunol. 2023 Jan 10:13:1084139. doi: 10.3389/fimmu.2022.1084139. eCollection 2022.

Authors

Xiaohe Zhou^{1

2}, Mingli Jiang^{1

2}, Fengjie Wang^{1

2}, Yuan Qian^{1

2}, Qinwei Song³, Yu Sun^{1

2}, Runan Zhu^{1

2}, Fang Wang^{1

2}, Dong Qu⁴, Ling Cao⁵, Lijuan Ma³, Yanpeng Xu^{1

2}, Ri De^{1

2}, Linqing Zhao^{1

2}

Affiliations

¹ Laboratory of Virology, Capital Institute of Pediatrics, Beijing, China.
² Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics, Beijing, China.
³ Clinical Laboratory, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
⁴ Intensive Care Unit, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing, China.
⁵ Department of Respiratory, Affiliated Children's Hospital, Capital Institute of Pediatrics, Beijing, China.

Abstract

Purpose: Immune 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.

Methods: The 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.

Results: The 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.

Conclusions: Diverse host immune responses were correlated with differential subtypes and genotypes of RSV in pediatric patients, demonstrating the impact of viral genetics on host immunity.

Keywords: antiviral effects; chemokines and cytokines; human respiratory syncytial virus; immune evasion; viral genetic differences.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Genotype
Humans
Immune Evasion*
Interleukin-1alpha
Palivizumab / pharmacology
Phylogeny
Respiratory Syncytial Virus Infections* / immunology
Respiratory Syncytial Virus, Human* / genetics

Substances

Interleukin-1alpha
Palivizumab

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81572035) and the Research Foundation of the Capital Institute of Pediatrics (CXYJ-2021-07).