Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan

Background Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV S region is an important public health problem halting preventive efforts. The aim of the current study was t...

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Main Authors: Nidaa A. Ababneh, Malik Sallam, Doaa Kaddomi, Abdelrahman M. Attili, Isam Bsisu, Nadia Khamees, Amer Khatib, Azmi Mahafzah
Format: Article
Language:English
Published: PeerJ Inc. 2019-03-01
Series:PeerJ
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Online Access:https://peerj.com/articles/6583.pdf
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author Nidaa A. Ababneh
Malik Sallam
Doaa Kaddomi
Abdelrahman M. Attili
Isam Bsisu
Nadia Khamees
Amer Khatib
Azmi Mahafzah
author_facet Nidaa A. Ababneh
Malik Sallam
Doaa Kaddomi
Abdelrahman M. Attili
Isam Bsisu
Nadia Khamees
Amer Khatib
Azmi Mahafzah
author_sort Nidaa A. Ababneh
collection DOAJ
description Background Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV S region is an important public health problem halting preventive efforts. The aim of the current study was to investigate patterns of HBV escape and resistance mutations and to assess domestic transmission of the virus. Methods Patients infected with HBV were recruited at Jordan University Hospital (n = 56) and were diagnosed during (1984–2012). A total of 37 partial HBV S sequences were generated using Sanger’s method. Mutation analysis was done using the HIV grade HBV drug resistance interpretation online tool and Geno2pheno (HBV) online tools. Domestic transmission of HBV was assessed using maximum likelihood phylogenetic inference with similar GenBank sequences. Results Genotyping revealed an exclusive presence of sub-genotype D1. Typical HBV escape mutants were identified in seven patients. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5–34.2]). Reverse transcriptase (RT) sequence analysis showed mutations in three patients with overall prevalence of 8.1% (95% CI [2.8–21.3]). RT mutations included: V173L, S202I, L180M, M204V and T184A. Transmission cluster analysis revealed a relatively high proportion of infections taking place as a result of domestic spread (29.7%). Conclusions Based on our findings, RT mutation analysis appears to be of high value before the initiation of therapy in patients with chronic HBV infection in Jordan. Phylogenetic analyses revealed a considerable proportion of local spread in the country which should be considered in the preventive infection control efforts.
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spelling doaj.art-8621bd80d14e4a31b8b2ea8e26c771b12023-12-03T10:36:18ZengPeerJ Inc.PeerJ2167-83592019-03-017e658310.7717/peerj.6583Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in JordanNidaa A. Ababneh0Malik Sallam1Doaa Kaddomi2Abdelrahman M. Attili3Isam Bsisu4Nadia Khamees5Amer Khatib6Azmi Mahafzah7Cell Therapy Center (CTC), University of Jordan, Amman, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, University of Jordan, Amman, JordanGastroenterology and Liver Division, Department of Internal Medicine, Jordan University Hospital, Amman, JordanSchool of Medicine, University of Jordan, Amman, JordanSchool of Medicine, University of Jordan, Amman, JordanGastroenterology and Liver Division, Department of Internal Medicine, Jordan University Hospital, Amman, JordanGastroenterology and Liver Division, Department of Internal Medicine, Jordan University Hospital, Amman, JordanDepartment of Pathology, Microbiology and Forensic Medicine, School of Medicine, University of Jordan, Amman, JordanBackground Hepatitis B virus (HBV) is an important infectious cause of morbidity and mortality in Jordan. HBV genotype D is the most prevalent in the country. Virus escape mutants in the HBV S region is an important public health problem halting preventive efforts. The aim of the current study was to investigate patterns of HBV escape and resistance mutations and to assess domestic transmission of the virus. Methods Patients infected with HBV were recruited at Jordan University Hospital (n = 56) and were diagnosed during (1984–2012). A total of 37 partial HBV S sequences were generated using Sanger’s method. Mutation analysis was done using the HIV grade HBV drug resistance interpretation online tool and Geno2pheno (HBV) online tools. Domestic transmission of HBV was assessed using maximum likelihood phylogenetic inference with similar GenBank sequences. Results Genotyping revealed an exclusive presence of sub-genotype D1. Typical HBV escape mutants were identified in seven patients. These mutations included: L109R, Q129R, M133L, S143L and D144E with overall prevalence of 18.9% (95% CI [9.5–34.2]). Reverse transcriptase (RT) sequence analysis showed mutations in three patients with overall prevalence of 8.1% (95% CI [2.8–21.3]). RT mutations included: V173L, S202I, L180M, M204V and T184A. Transmission cluster analysis revealed a relatively high proportion of infections taking place as a result of domestic spread (29.7%). Conclusions Based on our findings, RT mutation analysis appears to be of high value before the initiation of therapy in patients with chronic HBV infection in Jordan. Phylogenetic analyses revealed a considerable proportion of local spread in the country which should be considered in the preventive infection control efforts.https://peerj.com/articles/6583.pdfHepatitis BHBVMutationPhylogenyEpidemiology
spellingShingle Nidaa A. Ababneh
Malik Sallam
Doaa Kaddomi
Abdelrahman M. Attili
Isam Bsisu
Nadia Khamees
Amer Khatib
Azmi Mahafzah
Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
PeerJ
Hepatitis B
HBV
Mutation
Phylogeny
Epidemiology
title Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
title_full Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
title_fullStr Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
title_full_unstemmed Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
title_short Patterns of hepatitis B virus S gene escape mutants and reverse transcriptase mutations among genotype D isolates in Jordan
title_sort patterns of hepatitis b virus s gene escape mutants and reverse transcriptase mutations among genotype d isolates in jordan
topic Hepatitis B
HBV
Mutation
Phylogeny
Epidemiology
url https://peerj.com/articles/6583.pdf
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