Pre-S2 and HBV associated hepatocellular carcinoma

Abstract

Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma (HCC). Under selection pressures of host immunity and/or immunoprophylaxis and antiviral therapies, HBV evolves by accumulating mutations in its genome. Several studies highlighted the considerable importance of HBV surface (HBs) protein mutants (pre-S/S variants) in tumorigenesis. Among those mutants, pre-S2 mutants have been recognized as "precursor lesions of HCC" and as risk factors for post-operative recurrence of HCC. Pre-S2 mutants play important roles in tumor progression and induce various mechanisms of tumorigenesis. These roles include that the cytoplasmic orientation of the pre-S2 domain is essential for the transcriptional activator C-terminally truncated middle surface protein (MHBst) which participates in the development of hepatocellular carcinoma. Pre-S2 mutants may also play important roles in HBV tumorigenesis by inducing both endoplasmic reticulum stress-dependent and endoplasmic reticulum (ER) stress-independent pathways. Because HCC has poor prognosis and its incidence is increasing, methods for the prevention and treatment of HCC should be comprehensive. Emerging treatments based on ER stress may provide a new strategy.

In silico functional and structural characterization of hepatitis B virus PreS/S-gene in Iranian patients infected with chronic hepatitis B virus genotype D

“…The nucleotide substitutions in the pre-S1 promoter region, particularly the G2765A mutation, reduce the L protein expression and regulate the biological situation of HBV and result in a low viral load and then less serious disease in chronic HBV infection [12]. The mutations in pre-S2 may affect the signalling of the HBV-infected cells and increase tumorigenesis [13]. Mutations in pre-S regions have caused a decrease of binding affinity of monoclonal antibodies facing HBsAg and ended in the low expression of HBsAg.…”

The Role of DNA Viruses in Human Cancer

“…The preS2 protein activates c-Raf-1/Erk2 signaling and increases proliferation rate of hepatocytes (Figure 3). 66,67 In the late 1970s, an HBV vaccine was developed to prevent the spread of HBV infection and the progression of HBVassociated HCC. A number of HBV vaccines are available including Engerix-B R (GlaxoSmithKline), Shanvac-B R (Shantha Biotech), and Genevac BTM (Serum Institute).…”

“…The preS2 protein activates c-Raf-1/Erk2 signaling and increases proliferation rate of hepatocytes ( Figure 3 ). 66 , 67 …”

Characteristics of Hepatitis B Virus Genotype and Sub-Genotype in Hepatocellular Cancer Patients in Vietnam

“…These two types of mutations weren’t observed at initial infection but would appear during disease progression [ 24 ]. Several studies reported that the preS1/S2 region mutation is associated with HCC [ 7 , 25 , 26 ]. An attempt to develop a vaccine based on the preS1 region was also conducted [ 25 ].…”