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

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          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.

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          Most cited references46

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          MEGA6: Molecular Evolutionary Genetics Analysis version 6.0.

          We announce the release of an advanced version of the Molecular Evolutionary Genetics Analysis (MEGA) software, which currently contains facilities for building sequence alignments, inferring phylogenetic histories, and conducting molecular evolutionary analysis. In version 6.0, MEGA now enables the inference of timetrees, as it implements the RelTime method for estimating divergence times for all branching points in a phylogeny. A new Timetree Wizard in MEGA6 facilitates this timetree inference by providing a graphical user interface (GUI) to specify the phylogeny and calibration constraints step-by-step. This version also contains enhanced algorithms to search for the optimal trees under evolutionary criteria and implements a more advanced memory management that can double the size of sequence data sets to which MEGA can be applied. Both GUI and command-line versions of MEGA6 can be downloaded from www.megasoftware.net free of charge.
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            ICTV Virus Taxonomy Profile: Pneumoviridae.

            The family Pneumoviridae comprises large enveloped negative-sense RNA viruses. This taxon was formerly a subfamily within the Paramyxoviridae, but was reclassified in 2016 as a family with two genera, Orthopneumovirus and Metapneumovirus. Pneumoviruses infect a range of mammalian species, while some members of the Metapneumovirus genus may also infect birds. Some viruses are specific and pathogenic for humans, such as human respiratory syncytial virus and human metapneumovirus. There are no known vectors for pneumoviruses and transmission is thought to be primarily by aerosol droplets and contact. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Pneumoviridae, which is available at www.ictv.global/report/pneumoviridae.
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              Human thymic stromal lymphopoietin preferentially stimulates myeloid cells.

              The sequence of a novel hemopoietic cytokine was discovered in a computational screen of genomic databases, and its homology to mouse thymic stromal lymphopoietin (TSLP) suggests that it is the human orthologue. Human TSLP is proposed to signal through a heterodimeric receptor complex that consists of a new member of the hemopoietin family termed human TSLP receptor and the IL-7R alpha-chain. Cells transfected with both receptor subunits proliferated in response to purified, recombinant human TSLP, with induced phosphorylation of Stat3 and Stat5. Human TSLPR and IL-7Ralpha are principally coexpressed on monocytes and dendritic cell populations and to a much lesser extent on various lymphoid cells. In accord, we find that human TSLP functions mainly on myeloid cells; it induces the release of T cell-attracting chemokines from monocytes and, in particular, enhances the maturation of CD11c(+) dendritic cells, as evidenced by the strong induction of the costimulatory molecules CD40 and CD80 and the enhanced capacity to elicit proliferation of naive T cells.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                10 January 2023
                2022
                : 13
                : 1084139
                Affiliations
                [1] 1 Laboratory of Virology, Capital Institute of Pediatrics , Beijing, China
                [2] 2 Beijing Key Laboratory of Etiology of Viral Diseases in Children, Capital Institute of Pediatrics , Beijing, China
                [3] 3 Clinical Laboratory, Affiliated Children’s Hospital, Capital Institute of Pediatrics , Beijing, China
                [4] 4 Intensive Care Unit, Affiliated Children’s Hospital, Capital Institute of Pediatrics , Beijing, China
                [5] 5 Department of Respiratory, Affiliated Children’s Hospital, Capital Institute of Pediatrics , Beijing, China
                Author notes

                Edited by: Wei Yi, Beijing Ditan Hospital, Capital Medical University, China

                Reviewed by: Tongqing Zhou, National Institutes of Health (NIH), United States; Qiwei Zhang, Jinan University, China

                *Correspondence: Linqing Zhao, linqingz525@ 123456163.com ; Ri De, graceride@ 123456163.com

                †These authors have contributed equally to this work

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1084139
                9871593
                36703972
                ab5e459e-7821-4ec1-a1be-72b47f84f16f
                Copyright © 2023 Zhou, Jiang, Wang, Qian, Song, Sun, Zhu, Wang, Qu, Cao, Ma, Xu, De and Zhao

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 October 2022
                : 19 December 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 46, Pages: 13, Words: 6521
                Funding
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                Award ID: No. 81572035
                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).
                Categories
                Immunology
                Original Research

                Immunology
                human respiratory syncytial virus,viral genetic differences,antiviral effects,chemokines and cytokines,immune evasion

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