Polymorphic APOBEC3 modulates chronic hepatitis B in Moroccan population

Abstract

The cytidine deaminase apolipoprotein B mRNA editing catalytic subunit-3 (APOBEC3) induces G-to-A hypermutation in hepatitis B virus (HBV) genomes and operates as part of the innate antiviral immune system. We investigated the associations between the presence of APOBEC3 variants and HBV carriage in a case-control study in the Moroccan population. A polymorphic deletion affecting the APOBEC3B gene and the H186R variant of APOBEC3G were genotyped in 179 HBV chronic carriers and 216 healthy control subjects. In addition, to assess the overall impact of APOBEC3 deaminases on circulating HBV, we looked for hyperedited forms of the viral genome using the 3DPCR technique and analysed editing context. Data analysis showed that there was no significant difference in the frequencies of deleted APOBEC3B alleles (P = 0.261) or genotypes (P = 0.333) between patients with chronic hepatitis B and control subjects. By contrast, subjects bearing deleted genotype had a faster progression of liver disease than those with the insertion genotype (adjusted OR, 3.72; 95% CI, 0.38-36.12). The analysis of the APOBEC3G H186R polymorphism revealed that R/R genotype frequencies were not significantly different in HBV infected patients and in healthy subjects. 3DPCR was positive in 26 samples (14%) among 179. Amplified viral segments displayed monomorphic G>A transitions highly reminiscent of APOBEC3G activity. Most intriguingly, hemi/homozygous carriers of the APOBEC3B deletion had significantly lower virus loads than patients with the wild type (median 539 vs. 2213 IU/mL, P = 0.0023). This result suggests that genetic variations in APOBEC3 cytidine deaminases do not predispose to chronicity but may modulate the course of persistent HBV infection.

Role of the single deaminase domain APOBEC3A in virus restriction, retrotransposition, DNA damage and cancer

“…In a subsequent study, it was shown that the overexpression of A3A induced hypermutation in the HBV genome, although the levels of hypermutants were less than those introduced by A3G (Abe et al, 2009). A third study examined the correlation between deletion of the A3B gene and chronic HBV infections (Ezzikouri et al, 2013). These investigators observed that patients with the A3B-deleted genotype had lower virus burdens than those patients without the A3B-deletion phenotype (Ezzikouri et al, 2013).…”

“…A third study examined the correlation between deletion of the A3B gene and chronic HBV infections (Ezzikouri et al, 2013). These investigators observed that patients with the A3B-deleted genotype had lower virus burdens than those patients without the A3B-deletion phenotype (Ezzikouri et al, 2013). A3A has also been shown to inhibit the replication of papillomaviruses (Ahasan et al, 2015;Warren et al, 2015).…”

Association between polymorphisms of theAPOBEC3Ggene and chronic hepatitis B viral infection and hepatitis B virus-related hepatocellular carcinoma

“…A previous study investigated the relationship between rs8177832 and CHB in 179 HBV chronic carriers and 216 healthy control subjects in a Moroccan population[31]. The results showed that the G genotype tended to be associated with an increased risk of developing CHB ( P = 0.254).…”

The Role of Cytidine Deaminases on Innate Immune Responses against Human Viral Infections

“…Due to the A3B ability of restricting HBV, it has been suggested that this gene deletion can result in reduced viral clearance, culminating with persistent infection [97]. In other studies, the homozygosity status for the deletion was associated with mild liver fibrosis, but not with a chronic carrier status [95], and with faster progression of liver disease [98]. Homozygous individuals for this deletion have also been reported with an increased risk for HIV acquisition, for a higher viral set point and for progression to AIDS [94], yet no effect was found on susceptibility to HIV infection and AIDS in Japanese or Indian populations [96].…”