Analysis of hepatitis B virus X gene phylogeny, genetic variability and its impact on pathogenesis: Implications in Eastern Indian HBV carriers

Abstract

HBx genetic variability was explored in the Eastern Indian population with low HCC incidence. DNase I sensitive HBV DNA was detected in 53% samples, which differed significantly between clinical groups (P<0.001). HBV genotypes A (Aa/A1), C (Cs/C1) and D (D1, D2, D3, D5) were detected in 37.5%, 18.7% and 43.7% samples respectively. Population specific signature HBx residues A(36), V(88), S(101) in Aa/A1 and residues P(41), Q(110) in D5 were detected. Mutations T(127), M(130) and I(131) were detected in 66.7%, 91% and 75% of genotype A, C and D5 samples respectively. Very low occurrence of HCC associated mutations (V(5)M/L, P(38)S, and H(94)Y) and absence of C-terminal deletions were observed. Our study shows that HBV genotype associated clinically important HBx variations may evolve and act distinctly in different geo-ethnic populations. Further studies on HBx functions from the perspective of genetic variability are essential for the better understanding of the clinical significance of HBV.

Genetic Characterization of Hepatitis B Virus in Peripheral Blood Leukocytes: Evidence for Selection and Compartmentalization of Viral Variants with the Immune Escape G145R Mutation

“…Moreover, subgenotype Ae/A2 has not been detected in any of the group III serum HBV isolates in this study, despite the fact that they were extracted and amplified simultaneously with the PBL samples. In addition, a number of our other studies focused on serum HBV isolates, and in parallel or after this study, we have detected diverse HBV subgenotypes, namely, Aa/A1, Cs/C1, D1, D2, D3, and D5 (1,2,4,10,12,14), but subgenotype Ae/A2 with G145R was not detected, regardless of the fact that all of the studies were performed using the same experimental procedures, reagent sets, and laboratory facilities. These facts exclude the possibility that the detection of subgenotype Ae/A2, specifically in the PBL, across individuals in the present study was due to cross-contamination.…”

“…lowed by genotypes C (subgenotype Cs/C1) and A (subgenotype Aa/A1) in our study population (1,2,3,4,12). Specifically, the incidence of HBV genotype Aa/A1 (the Afro-Asian subgenotype of genotype A) in the sera was found to be about 8 and 11% among the incidentally detected asymptomatic HBsAg-negative HBV carriers (occult HBV infection) and HBsAg-positive HBV carriers, respectively (2, 13).…”

“…Analogous genetic regions of the envelope gene frequently have been targeted for similar studies in other viruses (28,38,40,43,45,50). Although the HBV x gene region shows considerable variability, the frequent loss and low genetic variability of this HBV region in our study population (3,12) restricts its use for the robust molecular evolutionary analysis of HBV. We highlighted earlier that the HBV surface genetic region is an ideal candidate for molecular evolutionary analysis studies (11).…”

A study on sequence variations in pre‐S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non‐B, non‐C hepatocellular carcinoma patients in Taiwan

“…[11][12][13][14][15][16] In addition, HBV genotypes/subgenotypes and their related mutations in the HBx genome have been reported to be associated with HCC. Datta et al 17 collected the available literature focused on the functional significance of different HBx substitutions, and they found that the amino acid substitutions at position 5 (L/M), 31 (A), 38 (S) and 42 (P) have been reported to be significantly associated with HCC development in chronic hepatitis B patients in a particular genotype/subgenotype. However, whether these molecular virological factors in occult HBVinfected HCC patients resemble those in HBsAg-positive HCC patients have not been elucidated.…”

“…In addition, several mutations in HBx gene region have been reported to be significantly associated with HCC development in a particular genotype/subgenotype. 17 However, it remained unclear whether these HBx substitutions were associated with occult HBV-infected HCC.…”