Analysis of Antigenic and Genetic Variability of G-protein of Respiratory Syncytial Virus Subgroup A Isolated in Korea over 8 Years(1990~1998)

ABSTRACT Human respiratory syncytial virus (HRSV) is the most important cause of acute respiratory disease in infants. Two major subgroups (A and B) have been identified based on antigenic differences in the attachment G protein. Antigenic variation between and within the subgroups may contribute to reinfections with these viruses by evading the host immune responses. To investigate the circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed the G protein genetic variability of subgroup B sequences isolated over a 45-year period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to 2004). Our study revealed that the HRSV-B evolutionary rate (1.95 × 10−3 nucleotide substitutions/site/year) is similar to that previously estimated for HRSV-A (1.83 × 10−3 nucleotide substitutions/site/year). However, natural HRSV-B isolates appear to accommodate more drastic changes in their attachment G proteins. The most recent common ancestor of the currently circulating subgroup B strains was estimated to date back to around the year 1949. The divergence between the two major subgroups was calculated to have occurred approximately 350 years ago. Furthermore, we have identified 12 positively selected sites in the G protein ectodomain, suggesting that immune-driven selective pressure operates in certain codon positions. HRSV-A and -B strains have similar phylodynamic patterns: both subgroups are characterized by global spatiotemporal strain dynamics, where the high infectiousness of HRSV permits the rapid geographic spread of novel strain variants.

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Genetic variability in the G protein gene of human respiratory syncytial virus isolated from the Campinas metropolitan region, Brazil

Journal of Medical Virology ◽

10.1002/jmv.21249 ◽

2008 ◽

Vol 80 (9) ◽

pp. 1653-1660 ◽

Cited By ~ 13

Author(s):

Luciana Helena Antoniassi da Silva ◽

Fernando Rosado Spilki ◽

Adriana Gut Lopes Riccetto ◽

Renata Servan de Almeida ◽

Emílio Carlos Elias Baracat ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Genetic Variability ◽

G Protein ◽

Protein Gene ◽

Human Respiratory Syncytial Virus ◽

Metropolitan Region ◽

Syncytial Virus

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The antigenic and genetic variability of bovine respiratory syncytial virus with emphasis on the G protein

Veterinární Medicína ◽

10.17221/5778-vetmed ◽

2012 ◽

Vol 48 (No. 9) ◽

pp. 254-266 ◽

Cited By ~ 5

Author(s):

V. Valentova

Keyword(s):

Respiratory Syncytial Virus ◽

Genetic Variability ◽

G Protein ◽

Viral Protein ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Clinical Symptoms ◽

Bovine Respiratory Syncytial Virus ◽

Th2 Response ◽

Syncytial Virus

Bovine respiratory syncytial virus (BRSV) and related human respiratory syncytial virus (HRSV) are major respiratory tract pathogens in calves and infants, respectively. Great attention is now paid to prevention of the disease caused by these agents. Glycoprotein G is the most variable viral protein and antigenic grouping of RSV isolates is based on distinct antigenic reactivity patterns determined with a set of G protein specific mAbs. Genetic variability of the G protein is used during epidemiology and epizootiology studies of HRSV and BRSV diseases, respectively. The constant genetic drift can be observed within G protein sequences. Both cell-mediated and antibody-mediated immune responses contribute to efficient protection against RSV infection. The neutralizing antibodies are induced by F and G proteins. The G protein fails to induce cytotoxic lymphocytes response and may causes aberrant Th2 response leading to enhancement of clinical symptoms in subsequently infected vaccines. The G as the most variable viral protein associated with immunopathologic effect is a critical factor in vaccine development.

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Molecular epidemiology of respiratory syncytial virus in The Gambia

Epidemiology and Infection ◽

10.1017/s0950268896001872 ◽

1999 ◽

Vol 122 (1) ◽

pp. 155-160 ◽

Cited By ~ 18

Author(s):

P. A. CANE ◽

M. WEBER ◽

M. SANNEH ◽

R. DACKOUR ◽

C. R. PRINGLE ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Genetic Variability ◽

G Protein ◽

Protein Gene ◽

The Gambia ◽

The World ◽

Rsv Infection ◽

Syncytial Virus ◽

The Uk ◽

Developed World

Respiratory syncytial virus (RSV) infection in The Gambia occurs seasonally in association with the rainy season. This study examined the genetic variability of RSV isolates from four consecutive epidemics from 1993–6. Each epidemic was made up of a number of variants which were replaced in subsequent epidemics. Analysis of attachment (G) protein gene sequences showed that isolates were closely related to those observed in the rest of the world. However, many isolates from 1993 and 1994 were unlike other isolates observed in the developed world during this period and were more similar to isolates from 1984 in Europe. In addition, the most commonly observed genotype in the UK in the 1990s was not detected in The Gambia during this period.

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Structural Characterization and Binding Studies of the Ectodomain G Protein of Respiratory Syncytial Virus Reveal the Crucial Role of pH with Possible Implications in Host–Pathogen Interactions

ACS Omega ◽

10.1021/acsomega.1c00800 ◽

2021 ◽

Author(s):

Abu Hamza ◽

Zoya Shafat ◽

Zahoor Ahmad Parray ◽

Malik Hisamuddin ◽

Wajihul Hasan Khan ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

G Protein ◽

Structural Characterization ◽

Crucial Role ◽

Binding Studies ◽

Host Pathogen Interactions ◽

Host Pathogen ◽

Syncytial Virus

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Positive Selection Results in Frequent Reversible Amino Acid Replacements in the G Protein Gene of Human Respiratory Syncytial Virus

PLoS Pathogens ◽

10.1371/journal.ppat.1000254 ◽

2009 ◽

Vol 5 (1) ◽

pp. e1000254 ◽

Cited By ~ 90

Author(s):

Viviane F. Botosso ◽

Paolo M. de A. Zanotto ◽

Mirthes Ueda ◽

Eurico Arruda ◽

Alfredo E. Gilio ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Amino Acid ◽

Positive Selection ◽

G Protein ◽

Protein Gene ◽

Human Respiratory Syncytial Virus ◽

Syncytial Virus

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CX3CR1 Engagement by Respiratory Syncytial Virus Leads to Induction of Nucleolin and Dysregulation of Cilia-related Genes

10.1101/2020.07.29.227967 ◽

2020 ◽

Author(s):

Christopher S. Anderson ◽

Tatiana Chirkova ◽

Christopher G. Slaunwhite ◽

Xing Qiu ◽

Edward E. Walsh ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Epithelial Cells ◽

G Protein ◽

Infected Individual ◽

The Elderly ◽

Lung Epithelial Cells ◽

Host Cells ◽

Ciliated Cells ◽

Transcriptional Changes ◽

Syncytial Virus

AbstractRespiratory syncytial virus (RSV) contains a conserved CX3C motif on the ectodomain of the G-protein. The motif has been indicated as facilitating attachment of the virus to the host initiating infection via the human CX3CR1 receptor. The natural CX3CR1 ligand, CX3CL1, has been shown to induce signaling pathways resulting in transcriptional changes in the host cells. We hypothesize that binding of RSV to CX3CR1 via CX3C leads to transcriptional changes in host epithelial cells. Using transcriptomic analysis, the effect of CX3CR1 engagement by RSV was investigated. Normal human bronchial epithelial (NHBE) cells were infected with RSV virus containing either wildtype G-protein, or a mutant virus containing a CX4C mutation in the G-protein. RNA sequencing was performed on mock and 4-days-post-infected cultures. NHBE cultures were also treated with purified recombinant wild-type A2 G-protein. Here we report that RSV infection resulted in significant changes in the levels 766 transcripts. Many nuclear associated proteins were upregulated in the WT group, including Nucleolin. Alternatively, cilia-associated genes, including CC2D2A and CFAP221 (PCDP1), were downregulated. The addition of recombinant G-protein to the culture lead to the suppression of cilia-related genes while also inducing Nucleolin. Mutation of the CX3C motif (CX4C) reversed these effects on transcription decreasing nucleolin induction and lessening the suppression of cilia-related transcripts in culture. Furthermore, immunohistochemical staining demonstrated decreases in in ciliated cells and altered morphology. Therefore, it appears that engagement of CX3CR1 leads to induction of genes necessary for RSV entry as well as dysregulation of genes associated with cilia function.ImportanceRespiratory Syncytial Virus (RSV) has an enormous impact on infants and the elderly including increased fatality rates and potential for causing lifelong lung problems. Humans become infected with RSV through the inhalation of viral particles exhaled from an infected individual. These virus particles contain specific proteins that the virus uses to attach to human ciliated lung epithelial cells, initiating infection. Two viral proteins, G-protein and F-protein, have been shown to bind to human CX3CR1and Nucleolin, respectively. Here we show that the G-protein induces Nucleolin and suppresses gene transcripts specific to ciliated cells. Furthermore, we show that mutation of the CX3C-motif on the G-protein, CX4C, reverses these transcriptional changes.

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Respiratory Syncytial Virus Grown in Vero Cells Contains a Truncated Attachment Protein That Alters Its Infectivity and Dependence on Glycosaminoglycans

Journal of Virology ◽

10.1128/jvi.00986-09 ◽

2009 ◽

Vol 83 (20) ◽

pp. 10710-10718 ◽

Cited By ~ 55

Author(s):

Steven Kwilas ◽

Rachael M. Liesman ◽

Liqun Zhang ◽

Edward Walsh ◽

Raymond J. Pickles ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

G Protein ◽

Cell Cultures ◽

Vero Cells ◽

Target Cells ◽

Apical Surface ◽

Virus Attachment ◽

C Terminus ◽

Syncytial Virus

ABSTRACT Human respiratory syncytial virus (RSV) contains a heavily glycosylated 90-kDa attachment glycoprotein (G). Infection of HEp-2 and Vero cells in culture depends largely on virion G protein binding to cell surface glycosaminoglycans (GAGs). This GAG-dependent phenotype has been described for RSV grown in HEp-2 cells, but we have found that it is greatly reduced by a single passage in Vero cells. Virions produced from Vero cells primarily display a 55-kDa G glycoprotein. This smaller G protein represents a post-Golgi compartment form that is lacking its C terminus, indicating that the C terminus is required for GAG dependency. Vero cell-grown virus infected primary well-differentiated human airway epithelial (HAE) cell cultures 600-fold less efficiently than did HEp-2 cell-grown virus, indicating that the C terminus of the G protein is also required for virus attachment to this model of the in vivo target cells. This reduced infectivity for HAE cell cultures is not likely to be due to the loss of GAG attachment since heparan sulfate, the primary GAG used by RSV for attachment to HEp-2 cells, is not detectable at the apical surface of HAE cell cultures where RSV enters. Growing RSV stocks in Vero cells could dramatically reduce the initial infection of the respiratory tract in animal models or in volunteers receiving attenuated virus vaccines, thereby reducing the efficiency of infection or the efficacy of the vaccine.

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