{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:32Z","timestamp":1760145512979,"version":"build-2065373602"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sub-Saharan African Network for TB\/HIV Research Excellence","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]},{"name":"Bill &amp; Melinda Gates Foundation","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]},{"name":"Fogarty International Center at the US National Institutes of Health","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]},{"name":"NIH","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]},{"name":"Trials of Excellence in Southern Africa","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]},{"name":"European Union","award":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"],"award-info":[{"award-number":["218770\/Z\/19\/Z","SANTHE 2.0","INV-033558","D43 TW009610","1G11TW012503-01","TESAIII","CSA2020NoE-3104 TESAIII"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The interaction of multiple viruses in one host is thought to enhance the development of mutations. However, the impact of hepatitis D virus (HDV) positivity on the development of unique hepatitis B virus (HBV) mutations among people living with human immunodeficiency virus (HIV) (PLWH) remains poorly understood in African countries, including Botswana. We used HBV sequences generated from the Botswana Combination Prevention Project (BCPP), which is the largest pair-matched cluster-randomized HIV trial in Botswana. Only participants with available HBV sequences (n = 55) were included in our study ([HIV\/HBV-positive (n = 50) and HIV\/HBV\/HDV-positive (n = 5)]. Geno2pheno was used to determine HBV genotypes, and HBV surface region sequences (all subgenotype A1) were aligned in AliView for mutational analysis, while the impact of mutations was assessed using Phyre2. Our results identified 182 common mutations between the two groups. In the HIV\/HBV\/HDV cohort, only three mutations (L95W, W156Q, C221Y) were classified as deleterious, with only L95W being the most frequent. In the HIV\/HBV cohort, four mutations (W199R, C221A, C221S, W223G) were also classified as deleterious. Our results demonstrate the presence of unique HBV mutations among the HIV\/HBV\/HDV-positive cohort. Functional characterization of these mutations is recommended to determine their effect on HDV.<\/jats:p>","DOI":"10.3390\/genes15080982","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T11:43:44Z","timestamp":1721907824000},"page":"982","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Hepatitis Delta Virus Infection on the Selection of Hepatitis B Surface Antigen Mutations"],"prefix":"10.3390","volume":"15","author":[{"given":"Kabo","family":"Baruti","sequence":"first","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone Private Bag 00704, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7606-0569","authenticated-orcid":false,"given":"Wonderful T.","family":"Choga","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone Private Bag 00704, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-2705","authenticated-orcid":false,"given":"Bonolo B.","family":"Phinius","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Gaborone Private Bag 00704, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basetsana","family":"Phakedi","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0282-0793","authenticated-orcid":false,"given":"Lynnette","family":"Bhebhe","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gorata G. A.","family":"Mpebe","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patience C.","family":"Motshosi","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9815-9088","authenticated-orcid":false,"given":"Tsholofelo","family":"Ratsoma","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3821-4592","authenticated-orcid":false,"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"},{"name":"Department of Pathology, Division of Medical Virology, Stellenbosch University, Cape Town 7535, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mosimanegape","family":"Jongman","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone Private Bag 00704, Botswana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-9684","authenticated-orcid":false,"given":"Motswedi","family":"Anderson","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"Africa Health Research Institute (AHRI), Durban 4013, South Africa"},{"name":"The Francis Crick Institute, London NW1 2BE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simani","family":"Gaseitsiwe","sequence":"additional","affiliation":[{"name":"Research Laboratory, Botswana Harvard Health Partnership, Gaborone Private Bag BO 320, Botswana"},{"name":"Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024, February 20). Hepatitis Delta Virus Fact Sheet. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-d."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jhep.2020.04.008","article-title":"The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis","volume":"73","author":"Stockdale","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jhep.2016.10.007","article-title":"Hepatitis delta-associated mortality in HIV\/HBV-coinfected patients","volume":"66","author":"Moradpour","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s13690-021-00693-2","article-title":"The global hepatitis delta virus (HDV) epidemic: What gaps to address in order to mount a public health response?","volume":"79","author":"Hayashi","year":"2021","journal-title":"Arch. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1097\/01.aids.0000180787.10553.b2","article-title":"Single (B or C), dual (BC or BD) and triple (BCD) viral hepatitis in HIV-infected patients in Madrid, Spain","volume":"19","author":"Arribas","year":"2005","journal-title":"AIDS"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(10)61931-9","article-title":"Hepatitis delta virus","volume":"378","author":"Hughes","year":"2011","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.5501\/wjv.v4.i2.36","article-title":"Molecular interactions between hepatitis B virus and delta virus","volume":"4","author":"Tacke","year":"2015","journal-title":"World J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1093\/cid\/ciu167","article-title":"Hepatitis delta is a major determinant of liver decompensation events and death in HIV-infected patients","volume":"58","author":"Vispo","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"974","DOI":"10.4314\/ahs.v17i4.4","article-title":"Low sero-prevalence of hepatitis delta antibodies in HIV\/ hepatitis B co-infected patients attending an urban HIV clinic in Uganda","volume":"17","author":"Katwesigye","year":"2017","journal-title":"Afr. Health Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1111\/jgh.14142","article-title":"Role of hepatitis B surface antigen in hepatitis B virus relapse after entecavir or tenofovir prophylaxis in patients undergoing cancer chemotherapy","volume":"33","author":"Kuo","year":"2018","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_11","first-page":"1","article-title":"Hepatitis B virus large surface protein: Function and fame","volume":"4","author":"Churin","year":"2015","journal-title":"HepatoBiliary Surg. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/jhep.2003.50310","article-title":"Kinetics of the immune response during HBV and HCV infection","volume":"38","author":"Bertoletti","year":"2003","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s12250-018-0070-x","article-title":"The Variability of Amino Acid Sequences in Hepatitis B Virus","volume":"34","author":"Cao","year":"2019","journal-title":"Virol. Sin."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000150412","article-title":"Hepatitis B surface antigen variation and protective immunity","volume":"38","author":"Howard","year":"1995","journal-title":"Intervirology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.3748\/wjg.v20.i24.7653","article-title":"Clinical implications of hepatitis B virus mutations: Recent advances","volume":"20","author":"Lazarevic","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3748\/wjg.v22.i1.145","article-title":"Overview of hepatitis B virus mutations and their implications in the management of infection","volume":"22","author":"Caligiuri","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.virusres.2016.10.002","article-title":"Higher prevalence of cancer related mutations 1762T\/1764A and PreS deletions in hepatitis B virus (HBV) isolated from HBV\/HIV co-infected compared to HBV-mono-infected Chinese adults","volume":"227","author":"Li","year":"2017","journal-title":"Virus Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.virol.2010.06.038","article-title":"HBV mutations in untreated HIV-HBV co-infection using genomic length sequencing","volume":"405","author":"Audsley","year":"2010","journal-title":"Virology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.antiviral.2011.10.018","article-title":"Precore\/core promoter mutations and hepatitis B virus genotype in hepatitis B and C dually infected patients treated with interferon-based therapy","volume":"93","author":"Hung","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_20","unstructured":"Organisation, W.H. (2024, January 10). Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. Available online: https:\/\/www.who.int\/publications-detail-redirect\/9789241549059."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3851\/IMP3060","article-title":"HIV Therapy with Unknown HBV Status is Responsible for Higher Rate of HBV Genome Variability in Ethiopia","volume":"22","author":"Belyhun","year":"2016","journal-title":"Antivir. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chambal, L.M., Gudo, E.S., Carimo, A., Real, R.C., Mabunda, N., Maueia, C., Vubil, A., Zicai, A.F., Bhatt, N., and Antunes, F. (2017). HBV infection in untreated HIV-infected adults in Maputo, Mozambique. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0190460"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1159\/000360940","article-title":"Mechanisms of hepatitis B virus resistance development","volume":"57","author":"Warner","year":"2014","journal-title":"Intervirology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e422","DOI":"10.1016\/S2352-3018(20)30103-X","article-title":"Population uptake of HIV testing, treatment, viral suppression, and male circumcision following a community-based intervention in Botswana (Ya Tsie\/BCPP): A cluster-randomised trial","volume":"7","author":"Wirth","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"ofac707","DOI":"10.1093\/ofid\/ofac707","article-title":"High Prevalence of Hepatitis B Virus Infection among People with HIV in Rural and Periurban Communities in Botswana","volume":"10","author":"Phinius","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/j.jiph.2023.08.011","article-title":"High prevalence of hepatitis delta virus among people with hepatitis B virus and HIV coinfection in Botswana","volume":"16","author":"Baruti","year":"2023","journal-title":"J. Infect. Public Health"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Phinius, B.B., Anderson, M., Mokomane, M., Gobe, I., Choga, W.T., Ratsoma, T., Phakedi, B., Mpebe, G., Ditshwanelo, D., and Musonda, R. (2023). Atypical Hepatitis B Virus Serology Profile\u2014Hepatitis B Surface Antigen-Positive\/Hepatitis B Core Antibody-Negative\u2014In Hepatitis B Virus\/HIV Coinfected Individuals in Botswana. Viruses, 15.","DOI":"10.3390\/v15071544"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1093\/bioinformatics\/btu531","article-title":"AliView: A fast and lightweight alignment viewer and editor for large datasets","volume":"30","author":"Larsson","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_29","unstructured":"(2024, May 23). Geno2pheno (hbv) v2.0. Available online: https:\/\/hbv.geno2pheno.org\/."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Anderson, M., Gaseitsiwe, S., Moyo, S., Wessels, M.J.C., Mohammed, T., Sebunya, T.K., Powell, E.A., Makhema, J., Blackard, J.T., and Marlink, R. (2015). Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-1096-4"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Huong, N.T.C., Trung, N.Q., Luong, B.A., Tram, D.B., Vu, H.A., Bui, H.H., and Le, H.P.T. (2022). Mutations in the HBV PreS\/S gene related to hepatocellular carcinoma in Vietnamese chronic HBV-infected patients. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0266134"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"gmr.15037582","DOI":"10.4238\/gmr.15037582","article-title":"Identification of a mutation in Hepatitis B virus surface antigen capable of evading ELISA screening","volume":"15","author":"Cui","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"13057","DOI":"10.1128\/JVI.01495-07","article-title":"Entry of hepatitis delta virus requires the conserved cysteine residues of the hepatitis B virus envelope protein antigenic loop and is blocked by inhibitors of thiol-disulfide exchange","volume":"81","author":"Sureau","year":"2007","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Liu, Y., Testa, J.S., Philip, R., Block, T.M., and Mehta, A.S. (2011). A Ubiquitin independent degradation pathway utilized by a hepatitis B virus envelope protein to limit antigen presentation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0024477"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Colagrossi, L., Salpini, R., Scutari, R., Carioti, L., Battisti, A., Piermatteo, L., Bertoli, A., Fabeni, L., Minichini, C., and Trimoulet, P. (2018). HDV Can Constrain HBV Genetic Evolution in HBsAg: Implications for the Identification of Innovative Pharmacological Targets. Viruses, 10.","DOI":"10.3390\/v10070363"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1128\/JVI.73.4.3351-3358.1999","article-title":"Mutations in the carboxyl-terminal domain of the small hepatitis b virus envelope protein impair the assembly of hepatitis delta virus particles","volume":"73","author":"Jenna","year":"1999","journal-title":"J. Virol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/8\/982\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:23:12Z","timestamp":1760109792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/8\/982"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["genes15080982"],"URL":"https:\/\/doi.org\/10.3390\/genes15080982","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2024,7,25]]}}}