Identification of a novel HKU4-related coronavirus in single-cell datasets and clade viral host analysis
Abstract HKU4-related coronaviruses (CoVs) are merbecoviruses related to Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV). In 2022 and 2023, two HKU4-related CoV strains were discovered inManis javanica(Malayan pangolin) metagenomic datasets derived from organ samples: HKU4-P251T and MjHKU4r-CoV-1. Together with theTylonycteris robustulabat CoV 162275, which was discovered in 2022, pangolin CoVs HKU4-P251T and MjHKU4r-CoV-1 form a novel phylogenetic clade distinct from all previously documented HKU4-related CoVs. In this study, we identified a novel HKU4-related CoV in a pangolin single-cell sequencing dataset generated by BGI-Shenzhen in Shenzhen, Guangdong, China in 2020. The CoV phylogenetically belongs to the same newly identified clade. The single cell datasets were reported as generated from organ samples of a single pangolin that died of natural causes. 98% of the HKU4-related CoV reads were found in only one of the seven single cell datasets — a large intestine cell dataset, cells of which exhibit low expression of DPP4. Bacterial contamination was found to be moderately correlated with HKU4-related CoV presence. We further identified with high confidence that the RNA-Seq dataset supporting one of four near identical variants of MjHKU4r-CoV-1 is aSus scrofa(wild pig) metagenomic dataset, with only a trace level ofManis javanicagenomic content. The presence of HKU4-related CoV reads in the dataset are almost certainly laboratory research-related and not from a premortal pangolin or pig infection. Our findings raise concerns about the provenance of the novel HKU4-related CoV we identify here, MjHKU4r-CoV-1 and its four near-identical variants..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 24. Juni Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jones, Adrian [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.06.18.545480 |
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| PPN (Katalog-ID): |
XBI039967913 |
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| 100 | 1 | |a Jones, Adrian |e verfasserin |0 (orcid)0000-0001-7355-0052 |4 aut | |
| 245 | 1 | 0 | |a Identification of a novel HKU4-related coronavirus in single-cell datasets and clade viral host analysis |
| 264 | 1 | |c 2023 | |
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| 520 | |a Abstract HKU4-related coronaviruses (CoVs) are merbecoviruses related to Middle Eastern Respiratory Syndrome coronavirus (MERS-CoV). In 2022 and 2023, two HKU4-related CoV strains were discovered inManis javanica(Malayan pangolin) metagenomic datasets derived from organ samples: HKU4-P251T and MjHKU4r-CoV-1. Together with theTylonycteris robustulabat CoV 162275, which was discovered in 2022, pangolin CoVs HKU4-P251T and MjHKU4r-CoV-1 form a novel phylogenetic clade distinct from all previously documented HKU4-related CoVs. In this study, we identified a novel HKU4-related CoV in a pangolin single-cell sequencing dataset generated by BGI-Shenzhen in Shenzhen, Guangdong, China in 2020. The CoV phylogenetically belongs to the same newly identified clade. The single cell datasets were reported as generated from organ samples of a single pangolin that died of natural causes. 98% of the HKU4-related CoV reads were found in only one of the seven single cell datasets — a large intestine cell dataset, cells of which exhibit low expression of DPP4. Bacterial contamination was found to be moderately correlated with HKU4-related CoV presence. We further identified with high confidence that the RNA-Seq dataset supporting one of four near identical variants of MjHKU4r-CoV-1 is aSus scrofa(wild pig) metagenomic dataset, with only a trace level ofManis javanicagenomic content. The presence of HKU4-related CoV reads in the dataset are almost certainly laboratory research-related and not from a premortal pangolin or pig infection. Our findings raise concerns about the provenance of the novel HKU4-related CoV we identify here, MjHKU4r-CoV-1 and its four near-identical variants. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Massey, Steven E. |4 aut | |
| 700 | 1 | |a Nemzer, Louis R. |0 (orcid)0000-0001-8861-0898 |4 aut | |
| 700 | 1 | |a Zhang, Daoyu |4 aut | |
| 700 | 1 | |a Deigin, Yuri |0 (orcid)0000-0002-3397-5811 |4 aut | |
| 700 | 1 | |a Quay, Steven C. |0 (orcid)0000-0002-0363-7651 |4 aut | |
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