Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts

Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity an...

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Main Authors: Rekha Khandia, Azmat Ali Khan, Noushad Karuvantevida, Pankaj Gurjar, Igor Vladimirovich Rzhepakovsky, Isabel Legaz
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Pathogens
Subjects:
Online Access:https://www.mdpi.com/2076-0817/12/2/325
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author Rekha Khandia
Azmat Ali Khan
Noushad Karuvantevida
Pankaj Gurjar
Igor Vladimirovich Rzhepakovsky
Isabel Legaz
author_facet Rekha Khandia
Azmat Ali Khan
Noushad Karuvantevida
Pankaj Gurjar
Igor Vladimirovich Rzhepakovsky
Isabel Legaz
author_sort Rekha Khandia
collection DOAJ
description Hepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.
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spelling doaj.art-6bd145b70c5140da8d6c8d70b23f9b8c2023-11-16T22:35:05ZengMDPI AGPathogens2076-08172023-02-0112232510.3390/pathogens12020325Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to HostsRekha Khandia0Azmat Ali Khan1Noushad Karuvantevida2Pankaj Gurjar3Igor Vladimirovich Rzhepakovsky4Isabel Legaz5Department of Biochemistry and Genetics, Barkatullah University, Bhopal 462026, IndiaPharmaceutical Biotechnology Laboratory, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaCollege of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai P.O. Box 505055, United Arab EmiratesDepartment of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, AustraliaMedical and Biological Faculty, North Caucasus Federal University, 355017 Stavropol, RussiaDepartment of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of Medicine, University of Murcia, 30120 Murcia, SpainHepatitis C virus (HCV) is enveloped RNA virus, encoding for a polyprotein that is processed by cellular proteases. The virus is responsible for liver cirrhosis, allograft rejection, and human hepatocellular carcinoma. Based on studies including compositional analysis, odds ratio analysis, parity analysis, skew analysis, relative synonymous codon usage, codon bias, and protein properties, it was evident that codon usage bias in HCV is dependent upon the nucleotide composition. Codon context analysis revealed CTC-CTG as a preferred codon pair. While CGA and CGT codons were rare, none of the codons were rare in HCV-like viruses envisaged in the present study. Many of the preferred codon pairs were valine amino acid-initiated, which possibly infers viral infectivity; hence the role of selection forces appears to act on the HCV genome, which was further validated by neutrality analysis where selection accounted for 87.28%, while mutation accounted for 12.72% force shaping codon usage. Furthermore, codon usage was correlated with the length of the genome. HCV viruses prefer valine-initiated codon pairs, while HCV-like viruses prefer alanine-initiated codon pairs. The HCV host range is very narrow and is confined to only humans and chimpanzees. Based on indices including codon usage correlation analysis, similarity index, and relative codon deoptimization index, it is evident in the study that the chimpanzee is the primary host of the virus. The present study helped elucidate the preferred host for HCV. The information presented in the study paved the way for generating an attenuated vaccine candidate through viral recoding, with finely tuned nucleotide composition and a perfect balance of preferred and rare codons.https://www.mdpi.com/2076-0817/12/2/325hepatitis C virus (HCV)codon usageliver cirrhosishepatocellular carcinomasimilarity indexrelative codon deoptimization index
spellingShingle Rekha Khandia
Azmat Ali Khan
Noushad Karuvantevida
Pankaj Gurjar
Igor Vladimirovich Rzhepakovsky
Isabel Legaz
Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
Pathogens
hepatitis C virus (HCV)
codon usage
liver cirrhosis
hepatocellular carcinoma
similarity index
relative codon deoptimization index
title Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
title_full Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
title_fullStr Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
title_full_unstemmed Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
title_short Insights into Synonymous Codon Usage Bias in Hepatitis C Virus and Its Adaptation to Hosts
title_sort insights into synonymous codon usage bias in hepatitis c virus and its adaptation to hosts
topic hepatitis C virus (HCV)
codon usage
liver cirrhosis
hepatocellular carcinoma
similarity index
relative codon deoptimization index
url https://www.mdpi.com/2076-0817/12/2/325
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