Background:
Botswana has an intermediate Hepatitis B virus (HBV) prevalence of 2–7%. To date, three HBV genotypes (A, D and E) have been reported in Botswana at the prevalence rates 80%, 18.6%, and 1.4%, respectively. However, the evolutionary history of all the identified genotypes within the population of Botswana remains unexplored. Such evolutionary analysis of HBV/D3 within Botswana population help in tracking disease evolution over time hence aiding in theoretical HBV prevention and management strategies. Our study first describes the origins, introductions (Time to Most Common Recent Ancestor (tMRCA), and evolutionary patterns of HBV sub-genotype D3 circulating in Botswana. Furthermore, we investigate the pairwise diversity on this sub-genotype and its spread within the population.
Methods:
Analysis was carried out using 69 available, HBV/D3 near-full-length sequences retrieved from the NCBI database of which 24 were from Botswana. Population dynamic analysis of the HBV/D3 (HBV/D3) sequences amongst people with HIV (PWH) was performed using the Bayesian coalescent model as implemented in BEAST2 software. The temporal signal was estimated through the root-to-tip method using node density in tempEst v1.5.3 and the correlation coefficient was used to indicate the amount of variation in genetic distance explained by sampling time. Skyline plots were used to estimate the effective HBV/D3 infections in Botswana population over time. Diversity analysis of Botswana sequences was done based on pairwise distances analysis implemented in MEGA v.7.0.1 software. Botswana sequences were partitioned into 7 HBV open reading frames (ORFs) and used to calculate nucleotide diversity.
Results:
HBV/D3 tMRCA amongst PLWH in Botswana dated back to 1964 (1839–1989), 95% Highest Posterior Density (HPD). Skyline plot showed a sharp increase in the number of HBV/D3 infections around the years 1999 and 2000 which is over the last approximately 22-23 years ago. The PreCore region had the highest median diversity of 0.02652 (IQR, 0.0115–0.05) and the surface (S) region was relatively conserved with median diversity of 0.0074 (IQR, 0.004–0.0134) p < 0.01.
Conclusions:
The study provides the first insights of HBV/D3 phylodynamic information in Botswana by predicting its tMRCA, origin and diversity thereby revealing the evolutionary dynamics of the HBV genotype. Diversity analysis showed that Core region was the most diverse region and confirmed that the surface region was the most conserved region.