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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866289/ https://www.ncbi.nlm.nih.gov/pubmed/36678391 http://dx.doi.org/10.3390/pathogens12010043 |
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author | Mukherjee, Sanket Kumar, Akhil Samal, Jasmine Gupta, Ekta Vivekanandan, Perumal Menon, Manoj B. |
author_facet | Mukherjee, Sanket Kumar, Akhil Samal, Jasmine Gupta, Ekta Vivekanandan, Perumal Menon, Manoj B. |
author_sort | Mukherjee, Sanket |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9866289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98662892023-01-22 Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution Mukherjee, Sanket Kumar, Akhil Samal, Jasmine Gupta, Ekta Vivekanandan, Perumal Menon, Manoj B. Pathogens Article 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. MDPI 2022-12-27 /pmc/articles/PMC9866289/ /pubmed/36678391 http://dx.doi.org/10.3390/pathogens12010043 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mukherjee, Sanket Kumar, Akhil Samal, Jasmine Gupta, Ekta Vivekanandan, Perumal Menon, Manoj B. Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9866289/ https://www.ncbi.nlm.nih.gov/pubmed/36678391 http://dx.doi.org/10.3390/pathogens12010043 |
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