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

Nidaa A Ababneh; Malik Sallam; Doaa Kaddomi; Abdelrahman M Attili; Isam Bsisu; Nadia Khamees; Amer Khatib; Azmi Mahafzah

doi:10.7717/peerj.6583

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

PeerJ. 2019 Mar 8:7:e6583. doi: 10.7717/peerj.6583. eCollection 2019.

Authors

Nidaa A Ababneh^#¹, Malik Sallam^#^{2

3

4}, Doaa Kaddomi⁵, Abdelrahman M Attili⁶, Isam Bsisu⁶, Nadia Khamees⁵, Amer Khatib⁵, Azmi Mahafzah^{2

3}

Affiliations

¹ Cell Therapy Center (CTC), University of Jordan, Amman, Jordan.
² Department of Pathology, Microbiology and Forensic Medicine, School of Medicine, University of Jordan, Amman, Jordan.
³ Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital, Amman, Jordan.
⁴ Department of Translational Medicine, Faculty of Medicine, Lund University, Malmö, Sweden.
⁵ Gastroenterology and Liver Division, Department of Internal Medicine, Jordan University Hospital, Amman, Jordan.
⁶ School of Medicine, University of Jordan, Amman, Jordan.

^# Contributed equally.

Abstract

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.

Keywords: Epidemiology; HBV; Hepatitis B; Mutation; Phylogeny.

Grants and funding

This work was supported by funding from the Deanship of Academic Research at the University of Jordan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.