Mutations in the fusion protein heptad repeat domains of human metapneumovirus impact on the formation of syncytia

Dubois, Julia; Cavanagh, Marie-Hélène; Terrier, B.; Hamelin, Marie‐Ève; Lina, Bruno; Shi, Rong; Rosa‐Calatrava, Manuel; Boivin, Guy

doi:10.1099/jgv.0.000796

Cited by 14 publications

(23 citation statements)

References 35 publications

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“…Peak viral titers of approximately 1 × 10 5 TCID 50 /mL for both the C-85473-WT and ∆SH-C-85473 viruses, or a peak of 4.22 × 10 4 TCID 50 /mL for the ∆G-C-85473 virus were reached by 4 dpi ( Figure 1C). According to previous studies with the viral C-85473 background [29,30], fluorescence microscopy showed that ∆SH-C-85473 and ∆G-C-85473 viruses harbored high viral spread and hyperfusogenic phenotypes, comparable to the WT rC-85473 ( Figure 1D).…”

Section: In Vitro Characteristics Of ∆Gand ∆Sh-hmpv Recombinant Virussupporting

confidence: 63%

“…In that regard, many HMPV subtypes co-circulate each year with high genetic diversity among A and B subtypes, particularly in the case of the less conserved G and SH proteins, with approximately 37% and 59% amino acid sequence homologies between subtypes, respectively [9,14]. In parallel, we and others previously demonstrated that HMPV viruses diverge in their in vitro and/or in vivo phenotypes in a strain-dependent manner, notably by considering the HMPV F and G proteins and their functions [18,[29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 61%

“…Based on our previous studies [29,30], we successfully generated by reverse genetics different GFP-expressing HMPV recombinant viruses derived from the A1/C-85473 strain (rC-85473, ∆G-C-85473, ∆SH-C-85473) and the B2/CAN98-75 strain (rCAN98-75, ∆G-CAN98-75 and ∆SH-CAN98-75) ( Figure 1A). Rescued recombinant viruses were firstly assessed for their replicative capacity in LLC-MK2 cells over a seven-day period ( Figure 1B,C).…”

Section: In Vitro Characteristics Of ∆Gand ∆Sh-hmpv Recombinant Virusmentioning

confidence: 99%

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Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

et al. 2019

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Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75. The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system.

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Section: In Vitro Characteristics Of ∆Gand ∆Sh-hmpv Recombinant Virussupporting

confidence: 63%

Section: Introductionmentioning

confidence: 61%

Section: In Vitro Characteristics Of ∆Gand ∆Sh-hmpv Recombinant Virusmentioning

confidence: 99%

See 1 more Smart Citation

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

et al. 2019

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“…Peak viral titers of approximately 1×10 5 TCID 50 /ml for both the C-85473-WT and ΔSH-C-85473 viruses, or a peak of 4.22×10 4 TCID 50 /ml for the ΔG-C-85473 virus were reached by 4 dpi ( Figure 1C ). According to previous studies with the viral C-85473 background [29, 30], fluorescence microscopy showed that ΔSH-C-85473 and ΔG-C-85473 viruses harbored high viral spread and hyperfusogenic phenotypes, comparable to the WT rC-85473 ( Figure 1D ).…”

Section: Resultssupporting

confidence: 61%

“…Based on our previous studies [29, 30], we successfully generated by reverse genetics different GFP-expressing HMPV recombinant viruses derived from the A1/C-85473 strain (rC-85473, ΔG-C-85473, ΔSH-C-85473) and the B2/CAN98-75 strain (rCAN98-75, ΔG-CAN98-75 and ΔSH-CAN98-75) ( Figure 1A ). Rescued recombinant viruses were firstly assessed for their replicative capacity in LLC-MK2 cells over a 7-day period ( Figure 1B-C ).…”

Section: Resultsmentioning

confidence: 99%

Strain-dependent impact of G and SH deletions provide new insights for live-attenuated HMPV vaccine development

Dubois

Pizzorno

Cavanagh

et al. 2019

Preprint

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Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with 23 currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have 24 been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. 25This approach showed promising outcomes but has not been evaluated further using different viral 26 strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro 27 fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. 28In this study, we investigated the putative contribution of the low conserved SH or G accessory 29 proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH-30 or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and 31 B2/CAN98-75. 32The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and 33 reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially 34 ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and 35 induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral 36 genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a 37 SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it 38 is both attenuated and protective in mice while being efficiently produced in a cell-based system. 40Keywords: human metapneumovirus (HMPV), live-attenuated vaccine (LAV), G protein, SH 41 protein, gene deletion, reverse genetics 42 43 44

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The effect of the HRB linker of Newcastle disease virus fusion protein on the fusogenic activity

Liu

Huang

et al. 2021

J Microbiol.

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Mutations in the fusion protein heptad repeat domains of human metapneumovirus impact on the formation of syncytia

Cited by 14 publications

References 35 publications

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

Strain-dependent impact of G and SH deletions provide new insights for live-attenuated HMPV vaccine development

The effect of the HRB linker of Newcastle disease virus fusion protein on the fusogenic activity

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