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Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt
BACKGROUND: Mutations within the “a” determinant region (position 124–147) that is present in the major hydrophilic region (MHR, position 99–160) of the hepatitis B surface antigen (HBsAg) are associated with vaccine-escape, lack of diagnosis, and failure to hepatitis B immunoglobulin (HBIG) therapy...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254413/ https://www.ncbi.nlm.nih.gov/pubmed/34234472 http://dx.doi.org/10.2147/IDR.S315299 |
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author | El-Mokhtar, Mohamed A Hetta, Helal F Mekky, Mohamed A Abd El-Kareem, Doaa M Ramadan, Mohammed Salah, Mohammed Mohamed, Nahed A El-Masry, Eman A Adel, Sara Sayed, Ibrahim M |
author_facet | El-Mokhtar, Mohamed A Hetta, Helal F Mekky, Mohamed A Abd El-Kareem, Doaa M Ramadan, Mohammed Salah, Mohammed Mohamed, Nahed A El-Masry, Eman A Adel, Sara Sayed, Ibrahim M |
author_sort | El-Mokhtar, Mohamed A |
collection | PubMed |
description | BACKGROUND: Mutations within the “a” determinant region (position 124–147) that is present in the major hydrophilic region (MHR, position 99–160) of the hepatitis B surface antigen (HBsAg) are associated with vaccine-escape, lack of diagnosis, and failure to hepatitis B immunoglobulin (HBIG) therapy. Data regarding the amino acid changes of “a” determinant region of HBsAg are limited in Egypt. The prevalence and mutations in this region among chronic HBV (CHB)-infected patients in Upper Egypt are not known. MATERIAL AND METHODS: Blood samples were collected from HBsAg-positive CHB-infected patients (n=123) admitted to Assiut University Hospitals. Serum samples were screened for HBsAg, HBeAg, anti-HBs and anti-HBe antibodies using commercially available ELISA kits. Viral load was determined by qPCR. In addition, mutational analysis was carried out targeting the HBV surface gene to determine the HBV genotype and vaccine escape mutations. RESULTS: Sequencing analysis of HBV DNA revealed that genotype D is the major circulating type (81.3%), followed by genotype E (18.7%). Analysis of the HBV genome revealed that 103/123 (83.7%) patients showed wild-type sequences and 20/123 (16.3%) showed mutations in the HBsAg gene. Mutation in seventeen patients (17/20, 85%) showed only one mutation, and three patients showed two mutations (3/20, 15%) in the “a” determinant region. The observed mutations were T115S (3/20, 15%), P120T/S (3/20, 15%), T126S (1/20, 5%), Q129R (2/20, 10%), M133T (2/20, 10%), S143L (5/20, 25%), D144E/A (3/20, 15%), and G145R/A (4/20, 20%). Mutations in the “a” determinant region were detected in genotype D isolates only. CONCLUSION: We described for the first time the prevalence and characterization of vaccine escape mutants in CHB patients in Upper Egypt. Mutational analysis of the “a” determinant region revealed the presence of a wide spectrum of mutants in the circulating HBV isolates that could be a potential threat to HBV diagnosis, therapy success, and HBV vaccination program in Upper Egypt. |
format | Online Article Text |
id | pubmed-8254413 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-82544132021-07-06 Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt El-Mokhtar, Mohamed A Hetta, Helal F Mekky, Mohamed A Abd El-Kareem, Doaa M Ramadan, Mohammed Salah, Mohammed Mohamed, Nahed A El-Masry, Eman A Adel, Sara Sayed, Ibrahim M Infect Drug Resist Original Research BACKGROUND: Mutations within the “a” determinant region (position 124–147) that is present in the major hydrophilic region (MHR, position 99–160) of the hepatitis B surface antigen (HBsAg) are associated with vaccine-escape, lack of diagnosis, and failure to hepatitis B immunoglobulin (HBIG) therapy. Data regarding the amino acid changes of “a” determinant region of HBsAg are limited in Egypt. The prevalence and mutations in this region among chronic HBV (CHB)-infected patients in Upper Egypt are not known. MATERIAL AND METHODS: Blood samples were collected from HBsAg-positive CHB-infected patients (n=123) admitted to Assiut University Hospitals. Serum samples were screened for HBsAg, HBeAg, anti-HBs and anti-HBe antibodies using commercially available ELISA kits. Viral load was determined by qPCR. In addition, mutational analysis was carried out targeting the HBV surface gene to determine the HBV genotype and vaccine escape mutations. RESULTS: Sequencing analysis of HBV DNA revealed that genotype D is the major circulating type (81.3%), followed by genotype E (18.7%). Analysis of the HBV genome revealed that 103/123 (83.7%) patients showed wild-type sequences and 20/123 (16.3%) showed mutations in the HBsAg gene. Mutation in seventeen patients (17/20, 85%) showed only one mutation, and three patients showed two mutations (3/20, 15%) in the “a” determinant region. The observed mutations were T115S (3/20, 15%), P120T/S (3/20, 15%), T126S (1/20, 5%), Q129R (2/20, 10%), M133T (2/20, 10%), S143L (5/20, 25%), D144E/A (3/20, 15%), and G145R/A (4/20, 20%). Mutations in the “a” determinant region were detected in genotype D isolates only. CONCLUSION: We described for the first time the prevalence and characterization of vaccine escape mutants in CHB patients in Upper Egypt. Mutational analysis of the “a” determinant region revealed the presence of a wide spectrum of mutants in the circulating HBV isolates that could be a potential threat to HBV diagnosis, therapy success, and HBV vaccination program in Upper Egypt. Dove 2021-06-28 /pmc/articles/PMC8254413/ /pubmed/34234472 http://dx.doi.org/10.2147/IDR.S315299 Text en © 2021 El-Mokhtar et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research El-Mokhtar, Mohamed A Hetta, Helal F Mekky, Mohamed A Abd El-Kareem, Doaa M Ramadan, Mohammed Salah, Mohammed Mohamed, Nahed A El-Masry, Eman A Adel, Sara Sayed, Ibrahim M Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title | Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title_full | Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title_fullStr | Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title_full_unstemmed | Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title_short | Characterization of Antigen Escape Mutations in Chronic HBV-Infected Patients in Upper Egypt |
title_sort | characterization of antigen escape mutations in chronic hbv-infected patients in upper egypt |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254413/ https://www.ncbi.nlm.nih.gov/pubmed/34234472 http://dx.doi.org/10.2147/IDR.S315299 |
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