Genetic alteration of human<i>MYH6</i>is mimicked by SARS-CoV-2 polyprotein: mapping viral variants of cardiac interest
Abstract Acute cardiac injury has been observed in a subset of COVID-19 patients, but the molecular basis for this clinical phenotype is unknown. It has been hypothesized that molecular mimicry may play a role in triggering an autoimmune inflammatory reaction in some individuals after SARS-CoV-2 infection. Here we investigate if linear peptides contained in proteins that are primarily expressed in the heart also occur in the SARS-CoV-2 proteome. Specifically, we compared the library of 136,704 8-mer peptides from 144 human proteins (including splicing variants) to 9,926 8-mers from all 17 viral proteins in the reference SARS-CoV-2 proteome. No 8-mers were exactly identical between the reference human proteome and the reference SARS-CoV-2 proteome. However, there were 45 8-mers that differed by only one amino acid when compared to the reference SARS-CoV-2 proteome. Interestingly, analysis of protein-coding mutations from 141,456 individuals showed that one of these 8-mers from the SARS-CoV-2 Replicase polyprotein 1a/1ab (KIALKGGK) is identical to aMYH6peptide encoded by the c.5410C>A (Q1804K) genetic variation, which has been observed at low prevalence in Africans/African Americans (0.08%), East Asians (0.3%), South Asians (0.06%) and Latino/Admixed Americans (0.003%). Furthermore, analysis of 4.85 million SARS-CoV-2 genomes from over 200 countries shows that viral evolution has already resulted in 20 additional 8-mer peptides that are identical to human heart-enriched proteins encoded by reference sequences or genetic variants. Whether such mimicry contributes to cardiac inflammation during or after COVID-19 illness warrants further experimental evaluation. We suggest that SARS-CoV-2 variants harboring peptides identical to human cardiac proteins should be investigated as ‘viral variants of cardiac interest’..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 16. Jan. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anand, Praveen [VerfasserIn] |
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| doi: |
10.1101/2021.11.23.469709 |
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| PPN (Katalog-ID): |
XBI033127433 |
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| 245 | 1 | 0 | |a Genetic alteration of human<i>MYH6</i>is mimicked by SARS-CoV-2 polyprotein: mapping viral variants of cardiac interest |
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| 520 | |a Abstract Acute cardiac injury has been observed in a subset of COVID-19 patients, but the molecular basis for this clinical phenotype is unknown. It has been hypothesized that molecular mimicry may play a role in triggering an autoimmune inflammatory reaction in some individuals after SARS-CoV-2 infection. Here we investigate if linear peptides contained in proteins that are primarily expressed in the heart also occur in the SARS-CoV-2 proteome. Specifically, we compared the library of 136,704 8-mer peptides from 144 human proteins (including splicing variants) to 9,926 8-mers from all 17 viral proteins in the reference SARS-CoV-2 proteome. No 8-mers were exactly identical between the reference human proteome and the reference SARS-CoV-2 proteome. However, there were 45 8-mers that differed by only one amino acid when compared to the reference SARS-CoV-2 proteome. Interestingly, analysis of protein-coding mutations from 141,456 individuals showed that one of these 8-mers from the SARS-CoV-2 Replicase polyprotein 1a/1ab (KIALKGGK) is identical to aMYH6peptide encoded by the c.5410C>A (Q1804K) genetic variation, which has been observed at low prevalence in Africans/African Americans (0.08%), East Asians (0.3%), South Asians (0.06%) and Latino/Admixed Americans (0.003%). Furthermore, analysis of 4.85 million SARS-CoV-2 genomes from over 200 countries shows that viral evolution has already resulted in 20 additional 8-mer peptides that are identical to human heart-enriched proteins encoded by reference sequences or genetic variants. Whether such mimicry contributes to cardiac inflammation during or after COVID-19 illness warrants further experimental evaluation. We suggest that SARS-CoV-2 variants harboring peptides identical to human cardiac proteins should be investigated as ‘viral variants of cardiac interest’. | ||
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| 700 | 1 | |a Lenehan, Patrick J. |e verfasserin |4 aut | |
| 700 | 1 | |a Niesen, Michiel |e verfasserin |4 aut | |
| 700 | 1 | |a Yoo, Unice |e verfasserin |4 aut | |
| 700 | 1 | |a Patwardhan, Dhruti |e verfasserin |4 aut | |
| 700 | 1 | |a Montorzi, Marcelo |e verfasserin |4 aut | |
| 700 | 1 | |a Venkatakrishnan, AJ |e verfasserin |4 aut | |
| 700 | 1 | |a Soundararajan, Venky |e verfasserin |4 aut | |
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