Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression

Abstract

Hepatitis B virus (HBV) reactivation occurs as a major complication of immunosuppressive therapy among persons who have recovered from acute hepatitis and those who have controlled chronic infection. Recent literature data emphasize the presence of a high degree of S gene variability in HBV isolates from patients who developed reactivation. In reactivated HBV, the most frequently detected mutations belong to the second loop of “a” determinant in HBsAg. These mutations were identified to be immune escape and responsible for vaccine- and diagnostic-escape phenomena. Their emergence clearly provides survival in the presence of a developed humoral immune response and is often associated with impaired serological diagnosis of HBV reactivation. The knowledge of their existence and roles can elucidate the process of reactivation and strongly highlights the importance of HBV DNA detection in monitoring all patients with a history of HBV infection who are undergoing immunosuppression. This review discusses the possible influence of the most frequently found immune-escape mutations on HBV reactivation.

Steroid Therapy and Steroid Response in Autoimmune Pancreatitis

“…The use of immunosuppressants, such as immunomodulators, rituximab, and corticosteroids, in patients with occult hepatitis B virus infection (serum anti-Hepatitis B surface (HBs) antibody positive or anti-Hepatitis B core (HBc) antibody positive and HBs antigen negative) should be carefully monitored by quantification of serum hepatitis B virus-DNA, as the virus can be reactivated by immunosuppressive agents [150].…”

Association of the Hepatitis B Virus Large Surface Protein with Viral Infectivity and Endoplasmic Reticulum Stress-mediated Liver Carcinogenesis

“…In addition to its location in the viral envelope, the surface protein is secreted outside cells through vesicle-mediated exocytosis to form filamentous and spherical SVPs that lack a genome-containing capsid; therefore, the HBV surface protein is a relatively stable biomarker indicating an infection history [ 17 ]. The viral surface protein also serves as a major epitope recognized by T cells, inducing T cell exhaustion through chronic stimulation and leading to failure of the immune surveillance machinery to recognize the virus [ 18 , 19 ]. To date, the molecular mechanisms by which the HBV surface protein triggers the disruption of the host immune response and by which it, in abundance, affects cellular functions through crosstalk with host factors, remain to be delineated.…”

“…The major serological determinants for HBsAg subtypes are at positions 122 and 160, in the antigenic loop spacer between TM2 and TM3. Mutations at these and some other residues in this protein region have been associated with viral immune escape and are critical for vaccine and diagnostic escape phenomena, revealing their critical effects for HBs antigenicity [ 18 , 36 ]. Moreover, to facilitate the viral entry, the (+)-charged Arg122 and Lys141 residues interact with the (−)-charged HSPGs on the cell surface [ 37 ].…”

Characterization of occult hepatitis B in high-risk populations in Kenya

“…Phylogenetic tree construction was optimized by nearest neighbour interchange and subtree pruning and regrafting with branch support computed by the approximate likelihood-ratio test based on a Shimodaira-Hasegawa-like procedure [27]. Nucleotide sequence alignments were translated to amino acid in order to determine the presence of mutations affecting susceptibility to antiviral therapies (any variant at reverse transcriptase amino acid sites rtI169, rtV173, rtL180, rtA181, rtT184, rtV191, rtA194, rtS202, rtM204 was noted) and immune recognition of the HBsAg protein (any variant at HBsAg amino acid sites P105, T116, T118, G119, K/R122, S/T123, C124, T/I126, P127, Q129, T/N131, M133, S136, C139, T140, K141, P142, S/T143, D144, G145, E164, P178, Q181, and I195 was noted) [28,29]. The risk of PCR environmental contamination was controlled with spatial and temporal separation of all steps (DNA extraction, PCR reaction pre-mix preparation, PCR amplification, and nested PCR analysis) as well as the inclusion of negative controls at the extraction and amplification steps.…”

“…MSM-SW OBI sequences were observed exclusively within Cluster 1, which clustered most closely with subgenotype A2 reference sequences with 98% branch support (Fig 1). Mutations associated with immune escape or impaired HBsAg or virion secretion [29] were infrequently observed within amino acid alignments of OBI sequences. Only three mutations were observed within the HBsAg major hydrophilic region (amino acids 99 to 160) of three specimens from jaundiced individuals; T116N, T118A (both observed with KN126 and KN160; accession numbers MK487143 and MK487142, respectively) and D144E (KN113; accession number MK487153).…”