Naturally Occurring Surface Antigen Variants of Hepatitis B Virus in Tunisian Patients

Abstract

In Tunisia, the prevalence of naturally occurring surface (S) gene variants of hepatitis B virus (HBV) has not been determined. In the present study, the prevalence of these variants was examined in terms of the clinical and viral state in a series of 99 Tunisian patients with HBV infection. The S genes were amplified and directly sequenced. Genotype D was predominant (98%), 40.4% isolates belonged to subgenotypes D7 and 1 to subgenotype D2. The most common subtype was ayw2 (95.9%). In total, 60.6% of the studied strains harbored S mutations. Several novel mutation patterns were detected. Interestingly, the presence of S mutations was significantly correlated with the D7 subgenotype, low HBV DNA and advancing age (≥35 years), and tended to be higher in liver cirrhosis than in chronic infection. The global prevalence of the major hydrophilic region variants was 12.1%, with substitution S143L/T as the most frequent (4%). Only 33.9% of S substitutions produced amino acid changes in the polymerase gene. In conclusion, a high prevalence of naturally occurring HBsAg variants was observed among Tunisian HBV carriers. Natural viral variability in a geographical region and duration of infection are among the major factors associated with the occurrence of S mutations.

Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks

“…The efficacy of mass vaccination programmes has been confirmed in other settings such as in The Gambia, where the prevalence of chronic hepatitis B was reduced from 12.4% to 0.8% [94,95,96]. In Tunisia, the universal immunisation programme has resulted in 68.9% of those immunised carrying the protection of levels of anti-HBs >10 mIU/mL into early adulthood [97], whereas a vaccine programme at 6, 10, and 14 weeks has resulted in sero-protection in 87% of immunised infants in South Africa [98]. Data from Taiwan importantly demonstrates the efficacy of a universal immunisation programme in reducing the longer-term risk of HCC [99].…”

Evolutionary dynamics of HBV‐D7 subgenotype in Tunisia

“…Recent studies reported predominance of genotype D (over 80%) with limited circulation of genotypes A, B, C, and E [Meldal et al, 2009;Hannachi et al, 2010;Ezzikouri et al, 2013]. HBV-D7 has been reported as one of the dominant subgenotype circulating in Tunisia [Meldal et al, 2009;Hannachi et al, 2010;Chaouch et al, 2016].…”

Identification of hepatitis B virus genotype I in Thailand

“…Examination of the amino acid sequences of the 9736409 open reading frames (ORFs) did not identify escape or resistance mutations in HBsAg or the polymerase. However, an early stop codon was identified in the HBsAg ORF at amino acid position 216 (T801A), which is a naturally occurring variant that results in a 10–amino‐acid truncation of the HBsAg ORF . While our direct amplicon sequencing method identified this variant as the major sequence present in 9736409, the possibility cannot be ruled out that a minor population of wildtype virus could produce full length HBsAg in this specimen.…”

“…However, an early stop codon was identified in the HBsAg ORF at amino acid position 216 (T801A), which is a naturally occurring variant that results in a 10-amino-acid truncation of the HBsAg ORF. 30 While our direct amplicon sequencing method identified this variant as the major sequence present in 9736409, the possibility cannot be ruled out that a minor population of wildtype virus could produce full length HBsAg in this specimen. In a comparison of all 39 HBV-I genomes with HBsAg and pre-C coverage, only one other strain (LA.KF214679, G668A) carried a nonsense HBsAg mutation, although it is unknown whether HBsAg was detectable in this specimen.…”