SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response

Abstract A new pandemic caused by the betacoronavirus SARS-CoV-2 originated in China in late 2019. Although often asymptomatic, a relevant percentage of affected people can develop severe pneumonia. Initial evidence suggests that dysregulation of the immune response could contribute to the pathogene...

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Autor principal:	Giovanni Franzo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8222e080d20640cd91025e0b779dceaf
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spelling	oai:doaj.org-article:8222e080d20640cd91025e0b779dceaf2021-12-02T16:51:31ZSARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response10.1038/s41598-021-90278-42045-2322https://doaj.org/article/8222e080d20640cd91025e0b779dceaf2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90278-4https://doaj.org/toc/2045-2322Abstract A new pandemic caused by the betacoronavirus SARS-CoV-2 originated in China in late 2019. Although often asymptomatic, a relevant percentage of affected people can develop severe pneumonia. Initial evidence suggests that dysregulation of the immune response could contribute to the pathogenesis, as previously demonstrated for SARS-CoV. The presence of genome composition features involved in delaying viral recognition is herein investigated for human coronaviruses (HCoVs), with a special emphasis on SARS-CoV-2. A broad collection of HCoVs polyprotein, envelope, matrix, nucleocapsid and spike coding sequences was downloaded and several statistics representative of genome composition and codon bias were investigated. A model able to evaluate and test the presence of a significant under- or over-representation of dinucleotide pairs while accounting for the underlying codon bias and protein sequence was also implemented. The study revealed the significant under-representation of CpG dinucleotide pair in all HcoV, but especially in SARS-CoV and even more in SARS-CoV-2. The presence of forces acting to minimize CpG content was confirmed by relative synonymous codon usage pattern. Codons containing the CpG pair were severely under-represented, primarily in the polyprotein and spike coding sequences of SARS-CoV-2. Additionally, a significant under-representation of the TpA pair was observed in the N and S region of SARS-CoV and SARS-CoV-2. Increasing experimental evidence has proven that CpG and TpA are targeted by innate antiviral host defences, contributing both to RNA degradation and RIG-1 mediated interferon production. The low content of these dinucleotides could contribute to a delayed interferon production, dysregulated immune response, higher viral replication and poor outcome. Significantly, the RIG-1 signalling pathway was proven to be defective in elderlies, suggesting a likely interaction between limited viral recognition and lower responsiveness in interferon production that could justify the higher disease severity and mortality in older patients.Giovanni FranzoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Giovanni Franzo SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
description	Abstract A new pandemic caused by the betacoronavirus SARS-CoV-2 originated in China in late 2019. Although often asymptomatic, a relevant percentage of affected people can develop severe pneumonia. Initial evidence suggests that dysregulation of the immune response could contribute to the pathogenesis, as previously demonstrated for SARS-CoV. The presence of genome composition features involved in delaying viral recognition is herein investigated for human coronaviruses (HCoVs), with a special emphasis on SARS-CoV-2. A broad collection of HCoVs polyprotein, envelope, matrix, nucleocapsid and spike coding sequences was downloaded and several statistics representative of genome composition and codon bias were investigated. A model able to evaluate and test the presence of a significant under- or over-representation of dinucleotide pairs while accounting for the underlying codon bias and protein sequence was also implemented. The study revealed the significant under-representation of CpG dinucleotide pair in all HcoV, but especially in SARS-CoV and even more in SARS-CoV-2. The presence of forces acting to minimize CpG content was confirmed by relative synonymous codon usage pattern. Codons containing the CpG pair were severely under-represented, primarily in the polyprotein and spike coding sequences of SARS-CoV-2. Additionally, a significant under-representation of the TpA pair was observed in the N and S region of SARS-CoV and SARS-CoV-2. Increasing experimental evidence has proven that CpG and TpA are targeted by innate antiviral host defences, contributing both to RNA degradation and RIG-1 mediated interferon production. The low content of these dinucleotides could contribute to a delayed interferon production, dysregulated immune response, higher viral replication and poor outcome. Significantly, the RIG-1 signalling pathway was proven to be defective in elderlies, suggesting a likely interaction between limited viral recognition and lower responsiveness in interferon production that could justify the higher disease severity and mortality in older patients.
format	article
author	Giovanni Franzo
author_facet	Giovanni Franzo
author_sort	Giovanni Franzo
title	SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
title_short	SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
title_full	SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
title_fullStr	SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
title_full_unstemmed	SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
title_sort	sars-cov-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8222e080d20640cd91025e0b779dceaf
work_keys_str_mv	AT giovannifranzo sarscov2andotherhumancoronavirusshowgenomepatternspreviouslyassociatedtoreducedviralrecognitionandalteredimmuneresponse
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SARS-CoV-2 and other human coronavirus show genome patterns previously associated to reduced viral recognition and altered immune response

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