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

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

Xiaohe Zhou  1   2 , Mingli Jiang  1   2 , Fengjie Wang  1   2 , Yuan Qian  1   2 , Qinwei Song  3 , Yu Sun  1   2 , Runan Zhu  1   2 , Fang Wang  1   2 , Dong Qu  4 , Ling Cao  5 , Lijuan Ma  3 , Yanpeng Xu  1   2 , Ri De  1   2 , Linqing Zhao  1   2
Affiliations

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

Xiaohe Zhou et al. Front Immunol. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The major surface glycoproteins F, G, and SH tertiary structures of RSV genotypes ON1, NA1, and BA9. In the trimer structure of G and F, each monomer was represented by one color(shown in pink, blue and green). SH of RSV-NA1 (green), RSV-ON1(wheat), and RSV-BA9 (blue) were displayed in the monomer. N-term: N-terminus; C-term: C-terminus; Antigenic site II (254-277 aa) of F: specific sites to Palivizumab. 24 aa duplicate insertion: the most significant structural changes in the HVR2 of G are shown in red boxes.
Figure 2
Figure 2
Comparison of cytokines and chemokines among respiratory specimens from patients infected with genotype ON1, NA1, or BA9 of RSV. I: the heat map. Each small square represents the specific value (pg/mL) of the cytokines and chemokines of each child. Different colors indicated the range of values of cytokines. For example, purple indicated the highest value, and red was the lowest. II: Significant differences were shown in the level of cytokines and chemokines (A: IL-17A; B: FIt-3L; C: IL-12P70; D: IL-12P40; E: IL-9; F: IL-4; G: IL-2; H: IFN-γ; I: IFN-α2) among respiratory samples from patients infected by genotype ON1, NA1, or BA9 of RSV. Each spot in the map represented the value (pg/mL) of the cytokines and chemokines of each patient. ●: samples from patients infected with genotype ON1; ■: samples from patients infected with genotype NA1; ▲: samples from patients infected with genotype BA9; *: significant differences were shown between the two groups (P<0.05). **: significant differences were shown between the two groups (P<0.01).
Figure 3
Figure 3
Comparison of cytokines and chemokines among the first serum samples from patients infected with genotype ON1, BA9 of RSV, or healthy children. I: the heat map. Each small square in the map represented the specific value (pg/mL) of the cytokines and chemokines of each child. Different colors indicated the range of values of cytokines. For example, purple indicated the highest value, and red was the lowest. II: Significant differences were shown in the level of cytokines and chemokines (A: MDC; B: Eotaxin) among the first serum group from patients infected by genotype ON1, BA9 of RSV, or healthy children. Each spot in the map represented the value (pg/mL) of the cytokines and chemokines of each child. ●: samples from healthy children; ■: samples from patients infected by genotype ON1; ▲: samples from patients infected by genotype BA9; *: significant differences were shown between the two groups (P<0.05). **: significant differences were shown between the two groups (P<0.01). ***: significant differences were shown between the two groups (P<0.001).
Figure 4
Figure 4
Comparison of cytokines and chemokines in the second serum group from patients infected with genotype ON1, BA9 of RSV, or healthy children. I: the heat map. Each small square in the heat map represented the specific value (pg/mL) of the cytokines and chemokines of each child. Different colors indicated the range of values of cytokines. For example, purple indicated the highest value, and red was the lowest. II: Significant differences were shown in the level of cytokines and chemokines (A: sCD40L; B: GM-CSF; C: TNFα; D: MIP-1β; E: IL-7; F: IL-3; G: IL-2; H: IL-1β; I: FIt-3L; J: Eotaxin) among the second serum group from patients infected with genotype ON1, BA9 of RSV, or healthy children. Each spot in the map represented the value (pg/mL) of the cytokines and chemokines of each patient. ●: samples from healthy children; ■: samples from patients infected by genotype ON1; ▲: samples from patients infected by genotype BA9; *: significant differences were shown between the two groups (P<0.05). ***: significant differences were shown between the two groups (P<0.001).
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