In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates
“…Genotypes B and C are common in Southeast Asia and China [ 18 – 20 ]. Some studies have shown that HBV of genotype C is more infectious and is associated with more serious liver disease, including LC and HCC [ 21 – 24 ].…”
Background
Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI.
Methods
Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism.
Results
Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure.
Conclusions
HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
“…Genotypes B and C are common in Southeast Asia and China [ 18 – 20 ]. Some studies have shown that HBV of genotype C is more infectious and is associated with more serious liver disease, including LC and HCC [ 21 – 24 ].…”
Background
Occult HBV infection (OBI) is a special form of hepatitis B virus (HBV) infection that may cause Liver cirrhosis and hepatocellular carcinoma, causing significant harm to patients. Given the insidious nature of OBI, it is usually not easy to be detected. Most of the samples currently studied are concentrated on blood donors, however, patients in this special state have not been fully studied. This project aimed to study the effect of HBV S region mutations on HBsAg in patients with clinical OBI.
Methods
Collect 107 HBsAg-/HBV DNA + blood samples from Beijing Youan Hospital, Capital Medical University from August 2022 to April 2023. Next, the successfully extracted and amplified HBV DNA S regions were sequenced. Construct mutant plasmids to verify the cell function of the high-frequency mutation sites and explore the possible molecular mechanism.
Results
Sixty-eight HBsAg-negative samples were sequenced, revealing high-frequency amino acid substitution sites in the HBV S protein, including immune escape mutations (i.e., sY100C、sK122R、sI126T、sT131P、and sS114T) and TMD (Transmembrane domain) region substitutions (i.e., sT5A、sG10D、sF20S、and sS3N). We constructed a portion of the mutant plasmids and found that sT5A, sF20S, sG10D, sS3N, sI68T, and sI126T single point mutations or combined mutations may decrease HBsAg expression or change the antigenicity of HBsAg leading to detection failure.
Conclusions
HBsAg-negative patients may show various mutations and amino acid replacement sites at high frequency in the HBV S-region, and these mutations may lead to undetectable Hepatitis B surface antigen (HBsAg), HBsAg antigenic changes or secretion inhibition.
“…In particular, genotype C circulates mainly in North China, Korea, Japan, and Thailand, and genotype B is predominant in South China and Southeast Asia [ 10 , 16 ]. Several studies have shown the enhanced infectivity of genotype C, and genotype C is associated with more severe liver diseases, including cirrhosis and HCC [ 17 , 18 ]. It was reported that HBV genotypes had a significant influence on the occurrence of OBI [ 5 ].…”
Introduction. The coexistence of hepatitis B virus (HBV) and hepatitis B surface antibodies (anti-HBs) in occult hepatitis B virus infection (OBI) is a contradictory phenomenon, and the underlying mechanism is not fully understood. The characteristics of pre-S/S mutations in OBI genotypes B and C (OBIB and OBIC) in the presence or absence of anti-HBs were analyzed extensively in this study. Methodology. The amino acid substitutions of envelope proteins of 21 OBI strains, including 4 HBs (+) OBIB, 6 HBs (−) OBIB, 6 HBs (+) OBIc, and 5 HBs (−) OBIC samples, were analyzed and fully compared among groups of HBV genotypes and the presence of anti-HBs. Results. The mutation rates in pre-S1, pre-S2, and S proteins of OBIC were significantly higher than wild-type HBV (wt-HBV) genotype C strains, but only the mutation rate of S protein in OBIB was significantly higher compared to wild-type HBV genotype B. The mutation rates in S protein of anti-HBs (−) OBI were higher than anti-HBs(+) OBI samples (4.40% vs. 2.43% in genotype B,
P
>
0.05
; 6.81% vs. 3.47% in genotype C,
P
<
0.05
). For these high-frequency substitutions in the pre-S/S region, the mutations sN40S and sK122R were found in 27.3% and 45.5% of anti-HBs (−) OBI strains, respectively. 7 substitutions were uniquely found in OBIC strains and 9 substitutions were commonly detected in OBIB and OBIC strains. Conclusions. These results suggested that the mutations might occur randomly and were not selected by antibody pressure.
“…Worldwide, it is estimated that more than 296 million people are chronically infected with HBV, which accounts for 820,000 deaths as a result of progressive liver diseases such as cirrhosis and HCC( Yardeni et al., 2023 ). In Southeast Asia and Sub-Saharan Africa, high hepatitis B surface antigen (HBsAg) seroprevalence is often linked to high levels of HBV-driven HCC incidence ( Liu et al., 2022 ; Sivasudhan et al., 2022 ). However, the molecular mechanisms of HBV-related HCC are not fully elucidated.…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.