Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution
Hepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/1/43 |
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| author | Sanket Mukherjee Akhil Kumar Jasmine Samal Ekta Gupta Perumal Vivekanandan Manoj B. Menon |
| author_facet | Sanket Mukherjee Akhil Kumar Jasmine Samal Ekta Gupta Perumal Vivekanandan Manoj B. Menon |
| author_sort | Sanket Mukherjee |
| collection | DOAJ |
| description | Hepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the context of CpG depletion. We analysed 2616 full-length HCV genomes from 1977 to 2021. During the four decades of evolution in humans, we found that HCV genomes have become significantly depleted in (a) CpG numbers, (b) CpG O/E ratios (i.e., relative abundance of CpGs), and (c) the number of ZAP-binding motifs. Interestingly, our data suggests that the loss of CpGs in HCV genomes over time is primarily driven by the loss of ZAP-binding motifs; thus suggesting a yet unknown role for ZAP-mediated selection pressures in HCV evolution. The HCV core gene is significantly enriched for the number of CpGs and ZAP-binding motifs. In contrast to the rest of the HCV genome, the loss of CpGs from the core gene does not appear to be driven by ZAP-mediated selection. This work highlights CpG depletion in HCV genomes during their evolution in humans and the role of ZAP-mediated selection in HCV evolution. |
| first_indexed | 2024-03-09T11:30:51Z |
| format | Article |
| id | doaj.art-c1583a5626e8423ca8b648bcd2bebd89 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T11:30:51Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-c1583a5626e8423ca8b648bcd2bebd892023-11-30T23:52:57ZengMDPI AGPathogens2076-08172022-12-011214310.3390/pathogens12010043Selective Depletion of ZAP-Binding CpG Motifs in HCV EvolutionSanket Mukherjee0Akhil Kumar1Jasmine Samal2Ekta Gupta3Perumal Vivekanandan4Manoj B. Menon5Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, IndiaKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, IndiaInstitute of Liver and Biliary Sciences, New Delhi 110070, IndiaInstitute of Liver and Biliary Sciences, New Delhi 110070, IndiaKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, IndiaKusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi 110016, IndiaHepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the context of CpG depletion. We analysed 2616 full-length HCV genomes from 1977 to 2021. During the four decades of evolution in humans, we found that HCV genomes have become significantly depleted in (a) CpG numbers, (b) CpG O/E ratios (i.e., relative abundance of CpGs), and (c) the number of ZAP-binding motifs. Interestingly, our data suggests that the loss of CpGs in HCV genomes over time is primarily driven by the loss of ZAP-binding motifs; thus suggesting a yet unknown role for ZAP-mediated selection pressures in HCV evolution. The HCV core gene is significantly enriched for the number of CpGs and ZAP-binding motifs. In contrast to the rest of the HCV genome, the loss of CpGs from the core gene does not appear to be driven by ZAP-mediated selection. This work highlights CpG depletion in HCV genomes during their evolution in humans and the role of ZAP-mediated selection in HCV evolution.https://www.mdpi.com/2076-0817/12/1/43HCVCpG depletionZAP-binding motifpathogenesisevolutionHCV core gene |
| spellingShingle | Sanket Mukherjee Akhil Kumar Jasmine Samal Ekta Gupta Perumal Vivekanandan Manoj B. Menon Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution Pathogens HCV CpG depletion ZAP-binding motif pathogenesis evolution HCV core gene |
| title | Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
| title_full | Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
| title_fullStr | Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
| title_full_unstemmed | Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
| title_short | Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
| title_sort | selective depletion of zap binding cpg motifs in hcv evolution |
| topic | HCV CpG depletion ZAP-binding motif pathogenesis evolution HCV core gene |
| url | https://www.mdpi.com/2076-0817/12/1/43 |
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