Hepatitis B Surface Antigen Could Contribute to the Immunopathogenesis of Hepatitis B Virus Infection

Abstract

Various findings concerning the clinical significance of quantitative changes in hepatitis B surface antigen (HBsAg) during the acute and chronic phase of hepatitis B virus (HBV) infection have been reported. In addition to being a biomarker of HBV-replication activity, it has been reported that HBsAg could contribute to the immunopathogenesis of HBV persistent infection. Moreover, HBsAg could become an attractive target for immune therapy, since the cellular and humeral immune response against HBsAg might be able to control the HBV replication and life cycle. However, several reports have described the immune suppressive function of HBsAg. HBsAg might suppress monocytes, dendritic cells (DCs), natural killer (NK), and natural killer T (NK-T) cells by direct interaction. On the other hand, cytotoxic T lymphocytes (CTLs) and helper T (Th) cells were exhausted by high amounts of HBsAg. In this paper, we focused on the immunological aspects of HBsAg, since better understanding of the interaction between HBsAg and immune cells could contribute to the development of an immune therapy as well as a biomarker of the state of HBV persistent infection.

Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent

“…One hallmark of CHB is the poor immune response to viral antigens (Ferrari, 2015;Ferrari et al, 1990;Jung et al, 1991). A major contributor to this is thought to be the persistent exposure of T cells to high levels of soluble viral antigens, resulting in a stepwise functional impairment and a phenomenon known as T-cell exhaustion (Bertoletti et al, 2009;Chisari and Ferrari, 1995;Kondo et al, 2013). Reducing the level of viral proteins may be one therapeutic strategy to overcome this.…”

“…Numerous studies have shown that persistent exposure of T cells to viral antigens is a major determinant of functional T-cell impairment in CHB (Bertoletti and Gehring, 2006;Boni et al, 2007;Op den Brouw et al, 2009;Wherry and Ahmed, 2004;Ye et al, 2015). HBsAg in particular may directly suppress monocytes, dendritic cells, and natural killer cells and lead to exhaustion of CD8 + and CD4 + T cells (Kondo et al, 2013). Evidence has also been gathered demonstrating the roles of HBeAg and, to a lesser extent, HBcAg in immune suppression (Milich et al, 1998;Riordan et al, 2006;Shimizu, 2012).…”

Hepatitis B virus antigens impair NK cell function

“…HBeAg is a secreted, nonparticulate form of the viral nucleocapsid, and the seropositivity of HBeAg is associated with a high risk of HCC [10]. In addition to be a biomarker of HBV-replication activity, it has been reported that HBsAg and HBeAg contributed to the immunopathogenesis of HBV persistent infection [11]. Woltman et al reported that HBeAg, especially HBsAg, was involved in the suppression of pDCs function and IFN-α production [12].…”

Prevalence of hepatitis B and C viruses among hemodialysis patients in Southern West Bank, Palestine

“…[8][9][10] Hepatitis B virion is a 42-nm particle comprising an electron-dense core (nucleocapsid) 27 nm in diameter surrounded by an outer envelope of the surface protein (HBsAg) embedded in membranous lipid derived from the host cell. 11,12 The nucleocapsid of the virion consists of the viral genome surrounded by the core antigen (HBcAg).…”

“…12 Hepatitis B virus produce hepatitis B core antigen (HBcAg), hepatitis B envelope antigen (HBeAg), hepatitis B x antigen (HBxAg), and hepatitis B surface antigen (HBsAg) that could contribute to the HBV life cycle. 9 In contrast the host immune system produce antibodies to these viral antigen. Anti-HBc and anti-HBs, and so different combinations of markers are used to identify different phases of HBV infection.…”