The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection

Elizabeth R. Davies; Kathryn A. Ryan; Kevin R. Bewley; Naomi S. Coombes; Francisco J. Salguero; Oliver T. Carnell; Sarah Biddlecombe; Michael Charlton; Amy Challis; Eleanor S. Cross; Alastair Handley; Didier Ngabo; Thomas M. Weldon; Yper Hall; Simon G.P. Funnell

doi:10.3390/v15051133

The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection

Elizabeth R. Davies^*, Kathryn A. Ryan, Kevin R. Bewley, Naomi S. Coombes, Francisco J. Salguero, Oliver T. Carnell, Sarah Biddlecombe, Michael Charlton, Amy Challis, Eleanor S. Cross, Alastair Handley, Didier Ngabo, Thomas M. Weldon, Yper Hall, Simon G.P. Funnell

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686–694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141–143).

Original language	English
Article number	1133
Journal	Viruses
Volume	15
Issue number	5
DOIs	https://doi.org/10.3390/v15051133
Publication status	Published - May 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

SARS-CoV-2
Syrian hamster
animal model
coronavirus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/v15051133

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Davies, E. R., Ryan, K. A., Bewley, K. R., Coombes, N. S., Salguero, F. J., Carnell, O. T., Biddlecombe, S., Charlton, M., Challis, A., Cross, E. S., Handley, A., Ngabo, D., Weldon, T. M., Hall, Y., & Funnell, S. G. P. (2023). The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection. Viruses, 15(5), Article 1133. https://doi.org/10.3390/v15051133

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title = "The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection",

abstract = "The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686–694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141–143).",

keywords = "SARS-CoV-2, Syrian hamster, animal model, coronavirus",

author = "Davies, {Elizabeth R.} and Ryan, {Kathryn A.} and Bewley, {Kevin R.} and Coombes, {Naomi S.} and Salguero, {Francisco J.} and Carnell, {Oliver T.} and Sarah Biddlecombe and Michael Charlton and Amy Challis and Cross, {Eleanor S.} and Alastair Handley and Didier Ngabo and Weldon, {Thomas M.} and Yper Hall and Funnell, {Simon G.P.}",

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year = "2023",

month = may,

doi = "10.3390/v15051133",

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Davies, ER, Ryan, KA , Bewley, KR , Coombes, NS , Salguero, FJ, Carnell, OT, Biddlecombe, S, Charlton, M, Challis, A, Cross, ES, Handley, A, Ngabo, D, Weldon, TM, Hall, Y & Funnell, SGP 2023, 'The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection', Viruses, vol. 15, no. 5, 1133. https://doi.org/10.3390/v15051133

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AU - Coombes, Naomi S.

AU - Salguero, Francisco J.

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AU - Biddlecombe, Sarah

AU - Charlton, Michael

AU - Challis, Amy

AU - Cross, Eleanor S.

AU - Handley, Alastair

AU - Ngabo, Didier

AU - Weldon, Thomas M.

AU - Hall, Yper

AU - Funnell, Simon G.P.

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N2 - The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686–694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141–143).

AB - The ongoing emergence of SARS-CoV-2 virus variants remains a source of concern because it is accompanied by the potential for increased virulence as well as evasion of immunity. Here we show that, although having an almost identical spike gene sequence as another Omicron variant (BA.5.2.1), a BA.4 isolate lacked all the typical disease characteristics of other isolates seen in the Golden Syrian hamster model despite replicating almost as effectively. Animals infected with BA.4 had similar viral shedding profiles to those seen with BA.5.2.1 (up to day 6 post-infection), but they all failed to lose weight or present with any other significant clinical signs. We hypothesize that this lack of detectable signs of disease during infection with BA.4 was due to a small (nine nucleotide) deletion (∆686–694) in the viral genome (ORF1ab) responsible for the production of non-structural protein 1, which resulted in the loss of three amino acids (aa 141–143).

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ER -

The Omicron Sub-Variant BA.4 Displays a Remarkable Lack of Clinical Signs in a Golden Syrian Hamster Model of SARS-CoV-2 Infection

Abstract

Bibliographical note

Keywords

UN SDGs

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