Molecular Characterization of Near Full-Length Genomes of Hepatitis B Virus Isolated from Predominantly HIV Infected Individuals in Botswana

Motswedi Anderson; Wonderful Tatenda Choga; Sikhulile Moyo; Trevor Graham Bell; Tshepiso Mbangiwa; Bonolo Bonita Phinius; Lynnette Bhebhe; Theresa Kibirige Sebunya; Shahin Lockman; Richard Marlink; Anna Kramvis; Max Essex; Rosemary Mubanga Musonda; Jason Tory Blackard; Simani Gaseitsiwe

doi:10.3390/genes9090453

Molecular Characterization of Near Full-Length Genomes of Hepatitis B Virus Isolated from Predominantly HIV Infected Individuals in Botswana

Genes (Basel). 2018 Sep 7;9(9):453. doi: 10.3390/genes9090453.

Authors

Motswedi Anderson^{1

2}, Wonderful Tatenda Choga³, Sikhulile Moyo^{4

5}, Trevor Graham Bell⁶, Tshepiso Mbangiwa^{7

8}, Bonolo Bonita Phinius⁹, Lynnette Bhebhe¹⁰, Theresa Kibirige Sebunya¹¹, Shahin Lockman^{12

13}, Richard Marlink^{14

15

16}, Anna Kramvis¹⁷, Max Essex^{18

19}, Rosemary Mubanga Musonda²⁰, Jason Tory Blackard²¹, Simani Gaseitsiwe^{22

23}

Affiliations

¹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
² Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana. [email protected].
³ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
⁴ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
⁵ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02138, USA. [email protected].
⁶ Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa. [email protected].
⁷ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
⁸ Faculty of Allied Health Sciences, University of Botswana, Gaborone, Botswana. [email protected].
⁹ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
¹⁰ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
¹¹ Department of Biological Sciences, Faculty of Science, University of Botswana, Gaborone, Botswana. [email protected].
¹² Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
¹³ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02138, USA. [email protected].
¹⁴ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
¹⁵ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02138, USA. [email protected].
¹⁶ Rutgers Global Health Institute, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA. [email protected].
¹⁷ Hepatitis Virus Diversity Research Unit (HVDRU), Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa. [email protected].
¹⁸ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
¹⁹ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02138, USA. [email protected].
²⁰ Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
²¹ College of Medicine, University of Cincinnati, Cincinnati, OH 45627, USA. [email protected].
²² Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. [email protected].
²³ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02138, USA. [email protected].

Abstract

The World Health Organization plans to eliminate hepatitis B and C Infections by 2030. Therefore, there is a need to study and understand hepatitis B virus (HBV) epidemiology and viral evolution further, including evaluating occult (HBsAg-negative) HBV infection (OBI), given that such infections are frequently undiagnosed and rarely treated. We aimed to molecularly characterize HBV genomes from 108 individuals co-infected with human immunodeficiency virus (HIV) and chronic hepatitis B (CHB) or OBI identified from previous HIV studies conducted in Botswana from 2009 to 2012. Full-length (3.2 kb) and nearly full-length (~3 kb) genomes were amplified by nested polymerase chain reaction (PCR). Sequences from OBI participants were compared to sequences from CHB participants and GenBank references to identify OBI-unique mutations. HBV genomes from 50 (25 CHB and 25 OBI) individuals were successfully genotyped. Among OBI participants, subgenotype A1 was identified in 12 (48%), D3 in 12 (48%), and E in 1 (4%). A similar genotype distribution was observed in CHB participants. Whole HBV genome sequences from Botswana, representing OBI and CHB, were compared for the first time. There were 43 OBI-unique mutations, of which 26 were novel. Future studies using larger sample sizes and functional analysis of OBI-unique mutations are warranted.

Keywords: Africa; Botswana; HBV; chronic hepatitis B; mutations; occult hepatitis B.

Abstract

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