Mannose-Binding Lectin in Chronic Hepatitis B Virus Infection *

Abstract

Mannose binding lectin (MBL) is a pattern-recognition molecule of the innate immune system. The roles of MBL and its gene (mbl2) polymorphisms, ؊221X/Y and codon 54A/B, in hepatitis B virus (HBV) infection were investigated in this study. We recruited 320 nonprogressed hepatitis B surface antigen (HBsAg) carriers; 199 progressed HBsAg carriers with hepatocellular carcinoma or cirrhosis; 87 spontaneously recovered individuals who were HBsAg negative and anti-HBs and anti HBc positive; and 484 controls who were naïve to HBV. There was no significant difference between nonprogressed carriers, spontaneously recovered individuals, and controls in terms of serum MBL levels and mbl2 polymorphisms distributions. However, the low MBL genotypes had a dose-dependent correlation with the cirrhosis and hepatocellular carcinoma in progressed carriers with odds ratios of 1.36 and 3.21 for the low and extremely low MBL genotypes, respectively (P ‫؍‬ .01). The lowexpression promoter haplotype XA (OR ‫؍‬ 1.97) and the mutant haplotype YB (OR ‫؍‬ 1.90) were also associated with the cirrhosis and hepatocellular carcinoma (P ‫؍‬ .002). As expected, the lower serum MBL levels in progressed carriers as compared with nonprogressed carriers were due to an overrepresentation of low and extremely low MBL genotypes. Moreover, MBL could bind HBsAg in a dose-and calcium-dependent and mannan-inhibitable manner in vitro, suggesting that binding occurs via the carbohydrate recognition domains. This binding also enhanced C4 deposition. In conclusion, these results suggest that low MBL genotypes associate with the occurrence of cirrhosis and hepatocellular carcinoma in progressed HBsAg carriers, and MBL can bind HBsAg. (HEPATOLOGY 2005;42:1037-1045

Specific interaction of hepatitis C virus glycoproteins with mannan binding lectin inhibits virus entry

“…MBL polymorphisms resulting in a deficiency of MBL have been linked with an increased risk of bacterial infections (Kilpatrick et al, 2003). More recently MBL deficiency has been identified as an important factor in the defense against hepatitis B virus infection (Chong et al, 2005). MBL has previously been shown to interact with a range of viruses, including HIV (Ying et al, 2004;Ji et al, 2005a), influenza (Anders et al, 1990;Malhotra et al, 1994) and Ebola (Ji et al, 2005b) viruses.…”

Potential Role of Mannose-Binding Lectin in Intrauterine Transmission of Hepatitis B Virus

“…The majority of studies revealed a correlation between MBL polymorphisms that confer low levels of MBL and poor prognoses such as viral persistence (9), disease progression (4,5,10), HBV acquisition (4) and survival in case of fulminant hepatic failure (6). However, some studies did not show any correlation between MBL polymorphisms and the prognosis of HBV infection (11) (as reviewed by Brown et al [3]).…”

Common variants of the TLR9 gene influence the clinical course of HBV infection

“…Mutations in the coding region of several human genes that profoundly affect the protein sequence and influence the course of hepatitis B have been described (23)(24)(25). As well, mutations in the promoter region of various genes influence the severity of HBV infection (26).…”