Association study between mannose-binding lectin haplotypes and X gene mutation of hepatitis B virus from treatment naïve patients.

Chenghao Su,Isabel Najera,Fernando Garcia-Alcalde,Lina Zhu,Jianjun Niu,Qianguo Mao,Daitze Wu,Yong Lin

doi:10.18632/aging.101097

Abstract

Mannose binding lectin (MBL) plays important role in the innate immunity of human. Mutations in the MBL2 gene can significantly change the serum level of MBL, and consequently alter the susceptibility and progression of infectious disease. However, the association between the MBL2 profile and the HBV mutation and quasispecies complexity has not yet been reported. Our approach includes the study of the MBL2 gene genotype as well as ultra-deep sequencing of the HBV viruses obtained from the plasma of 50 treatment naïve patients with chronic HBV infection. We found that the liver function was better among patients within the high MBL2 group with respect to those within the medium/low MBL2 group. Likewise, the number of mutations in the HBV X gene as well as the viral quasispecies complexity were significantly higher in medium/low MBL2 production group. Nucleotide substitution rates were also higher within the medium/low MBL2 production group in all positions described to have an influence in liver cancer development, except for A1499G. In this work we show that the MBL2 profile may have an impact on the HBV X gene mutations as well as on viral quasispecies complexity.

Highlights

Mannose binding lectin (MBL) in humans is capable of activating the complement system, triggering the immune response of MBL-associated serine protease (MASP)
Phase 2.1 employs Bayesian algorithm to estimate the haplotype for each patient, and the results showed that among 50 subjects, 22 (44%) were assigned to high MBL2 group and 28 (56%) were classified as medium/low MBL2 group in accordance with the classification criteria reported in method section
Our study investigated the relationship between human MBL2 haplotypes and the hepatitis B virus (HBV) X gene mutation profile, the nucleotide substitution rate of X gene, and viral quasispecies complexity

Summary

Introduction

Mannose binding lectin (MBL) in humans is capable of activating the complement system, triggering the immune response of MBL-associated serine protease (MASP). MBL can recognize and bind carbohydrate patterns which can be found on a large amount of pathogenic micro-organisms, including bacteria and viruses. The mutations of MBL2 gene, especially the structural variations in exon 1, can significantly reduce the level of functional MBL2 level in human serum by disrupting the collagenous structure of the protein [1]. The distribution of haplotypes constructed by these MBL2 polymorphisms vary among different races, the difference on MBL2 serum level can be observed between and within population [2]. The MBL2 deficiency caused by these polymorphisms can seriously compromise the innate immunity and closely associated with susceptibility and resistance to infection by pathogens [3], including hepatitis B virus (HBV)

Methods

Results

Conclusion