Genetic Diversity of the Hepatitis B Virus Strains in Cuba: Absence of West-African Genotypes despite the Transatlantic Slave Trade

Abstract

Cuba is an HBsAg low-prevalence country with a high coverage of anti-hepatitis B vaccine. Its population is essentially the result of the population mix of Spanish descendants and former African slaves. Information about genetic characteristics of hepatitis B virus (HBV) strains circulating in the country is scarce. The HBV genotypes/subgenotypes, serotypes, mixed infections, and S gene mutations of 172 Cuban HBsAg and HBV-DNA positive patients were determined by direct sequencing and phylogenetic analysis. Phylogenetic analysis of HBV S gene sequences showed a predominance of genotype A (92.4%), subgenotype A2 (84.9%) and A1 (7.6%). Genotype D (7.0%) and subgenotype C1 (0.6%) were also detected but typical (sub)genotypes of contemporary West-Africa (E, A3) were conspicuously absent. All genotype A, D, and C strains exhibited sequence characteristics of the adw2, ayw2, and adrq serotypes, respectively. Thirty-three (19.1%) patients showed single, double, or multiple point mutations inside the Major Hydrophilic domain associated with vaccine escape; eighteen (10.5%) patients had mutations in the T-cell epitope (amino acids 28-51), and there were another 111 point mutations downstream of the S gene. One patient had an HBV A1/A2 mixed infection. This first genetic study of Cuban HBV viruses revealed only strains that were interspersed with strains from particularly Europe, America, and Asia. The absence of genotype E supports previous hypotheses about an only recent introduction of this genotype into the general population in Africa. The presence of well-known vaccine escape (3.5%) and viral resistance mutants (2.9%) warrants strain surveillance to guide vaccination and treatment strategies.

Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy

“…This corroborates the important role of the immune response in the resolution of the infection. Interestingly, in a study performed by Rodriguez Lay et al [32] on HBV strains in Cuba, mutations associated with immune escape within the S gene from HBV genotype A1, A2, C1 were also frequently reported in the B cell epitope aa 124-147 and in the MHR. These data globally suggest that the 'a' determinant, as the immunodominant region of HBsAg stabilized by a conserved disulphide bridge of cysteine residues, can play a role in HBsAg persistence or clearance.…”

Molecular characterization of hepatitis B virus in Bangladesh reveals a highly recombinant population

“…The preS2/S1 regions were analyzed for preS1 deletion, preS1 mutations (A2962G, C3026A/T, C2964A, and C3116T), preS2 start codon deletion, and preS2 mutations (T53C). The S gene was analyzed for mutations in major hydrophilic region (MHR) (99aa-169aa) including the “a” determinant region (Y/L100C/I, Q101H/R, T113S, T115N, I/T126S/N, T127P, A128V, A143L, G145R, R160K, Y161F, E164D, and A168V), and other mutations associated with increased risk of HCC (N3S, R24K, P56Q, P62L, F85C, L126T/S, A168V, V184A, and S204R) [ 22 – 25 ] [ 26 ] [ 27 ]. Mutations in BCP (C1653T, T1753C, G1757A, A1762T, G1764A, C1766G, and T1768A), and the PC/core region associated with HCC (G1896A, G1899A, A2159G and A2189C/T, and G2203A/T) were also analyzed.…”

Temporal and geographic spreading of hepatitis B virus genotype A (HBV‐A) in Brazil and the Americas

“…8,9 Further, HBV-A1 and HBV-A2 are usually the only subgenotypes detected in most countries. 11,[13][14][15][16][17] HBV-A has a long evolutionary history with a common ancestor of more than one thousand years ago. 18 The two main subgenotypes (HBV-A1 and HBV-A2) seem to have emerged in two different continents: Africa and Europe.…”

“…9,11,12 In Latin America, HBV-A is the main genotype in Brazil (58.7%), Cuba (92.5%), Haiti (71.0%) and Panama (54.6%). [11][12][13][14] Also, this genotype has a high whole-genome genetic diversity, being classified into seven different subgenotypes (A1 to A7). Most of these subgenotypes are rare and restricted to very specific geographic regions, but HBV-A1 and HBV-A2 are more widespread and frequently detected in different countries.…”