Mannan binding lectin and viral hepatitis.
Mannan binding lectin (MBL) is a pattern recognition molecule of the innate immune system that binds to sugars on the surface of invading micro-organisms. Target binding, complement activation and other functions of MBL are dependent on the presence of multiple carbohydrate recognition domains. Several polymorphisms in the promoter and structural regions of MBL2 adversely affect the plasma concentration and oligomeric state of MBL. The possession of mutant alleles has been linked to disease outcome for a variety of bacterial and viral infections. Viral hepatitis is caused by unrelated viruses referred to as hepatitis virus A-E. The disease usually has both acute and chronic phases, the latter leading to cirrhosis and hepatocellular carcinoma. Hepatitis viruses B and C (HBV and HCV, respectively) are a significant cause of morbidity worldwide. HBV encodes envelope glycoproteins termed large, middle, and small that may exist in glycosylated or unglycosylated forms on the virion. An interaction between HBV glycoproteins and MBL has been demonstrated in vitro. Significant associations between MBL levels, determined by MBL2 haplotypes, and HBV persistence and disease progression have been described. HCV encodes two highly glycosylated envelope proteins, E1 and E2, which are potential targets for interaction with MBL. Mutant MBL2 haplotypes have been linked to disease progression and response to therapy in HCV infection. Here we summarise the effect of MBL2 polymorphisms on MBL function and how this may relate to disease outcome in HBV and HCV infection.
Brown
Kristelle S
KS
Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Ryder
Stephen D
SD
Irving
William L
WL
Sim
Robert B
RB
Hickling
Timothy P
TP
D016174:Hepacivirus / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D006525:Hepatitis, Viral, Human / Q000276:immunology*; D006801:Humans; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000502:physiology*; D011110:Polymorphism, Genetic
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin