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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...

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Autores principales: Mukherjee, Sanket, Kumar, Akhil, Samal, Jasmine, Gupta, Ekta, Vivekanandan, Perumal, Menon, Manoj B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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