Hepatitis B Virus Research in South Africa

Abstract

Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA despite the introduction of an infant immunization program implemented in 1995 and the availability of effective treatment for chronic HBV infection. In addition, the high prevalence of HIV infection amplifies HBV replication, predisposes patients to chronicity, and complicates management of the infection. HBV research has made significant progress leading to better understanding of HBV epidemiology and management challenges in the SA context. This has led to recent revision of the national HBV infection management guidelines. Research on developing new vaccines and therapies is underway and progress has been made with designing potentially curative gene therapies against HBV. This review summarizes research carried out in SA on HBV molecular biology, epidemiology, treatment, and vaccination strategies.

Keywords: HBV; HBV/HIV co-infection; gene therapy; occult HBV infection; vaccination.

Figure 1

Gene therapy tools used for targeted disruption of HBV replication in South Africa. (A) RNAi activators such as short hairpin RNAs (shRNAs), artificial primary microRNAs (apri-miRNAs), and short interfering RNAs (siRNAs) targeting hepatitis B x (HBx) sequence were designed and delivered using adenoviral vectors (AdVs), AdVs/lentiviral vectors (LVs)/adeno-associated viral vectors (AAVs) and liposomes, respectively. (B) Transcription activator-like effector endonucleases (TALENS) targeting Core or Surface and Transcription activator-like repressors (rTALEs) targeting Surface were generated and delivered as naked plasmid DNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) with CRISPR-associated (Cas) RNA-guided nucleases (CRISPR/c as) targeting Surface were designed and delivered using AAVs (Created with biorender.com).