《中国病毒病杂志》  2011年02期 92-98   出版日期:2011-04-01   ISSN:2095-0136   CN:11-5969/R
 甘露糖结合凝集素与人类免疫缺陷病毒感染的关联性研究


 

Mannose-binding lectin (MBL) is a circulating pattern recognition molecule involved in the innate immune system that mediates phagocytosis and activates compement by binding to a carbohydrate extremity[1-4]. However, MBL function is directly associated with its serum concentrations which are determined by the interplay between promoter and structural gene mutations[5, 6].

MBL2 variants at the following nucleotide positions affect MBL levels: 2 single nucleotide polymorphisms at promoter positions -550G/C (H/L variant) and -221G/C (X/Y variant), 1 in 5’ untranslated region +4C/T (P/Q variant) and 3 genetic variants at codons 52, 54 and 57 in exon 1 at nucleotide positions 223C/T(Arg52Cys, A/D allele), 230G/A (Gly54Asp, A/B allele), and 239G/A (Gly57Glu, A/C allele), respectively. MBL2 exon 1 variants result in single amino acid changes affecting oligomerization of MBL. Homozygous wild-type (A/A) sera contain predominantly fully functional MBL, whereas homozygous mutant sera (any combination of B, C, or D alleles) contain mostly low-molecular-weight MBL. Sera containing heterozygous variant alleles (A/O, O 5 B, C, or D) contain both high-molecular-weight and low-molecular-weight MBL, with the ratio determined by the promoter type on the normal haplotype (A allele)[7-9].

Entry of HIV into the target cells is mediated by the glycoproteins gp120 and gp41 which are present on the viral envelope. They sequentially bind to cellular receptor protein CD4 and also to co-receptor CXCR4 and/or CCR5. Both gp120 and gp41 are heavily glycosylated[10-12]. gp120 consists of glycans for almost 50% of its molecular weight. MBL could bind to gp120 and lead to the destruction or clearance of HIV by complement activation and opsonophagocytosis[13-16]. Furthermore, MBL could inhibit the HIV infection of T cells mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin[16, 17].

This study investigated the influence of MBL2 variants on HIV-1 infection and the association between these MBL polymorphisms, serum levels of MBL, and HIV-1 infection in Chinese Han population. In addition, CD4+ T-cell counts and viral load of 91 HIV-1 infected patients were detected. We hypothesized that variants in MBL2 gene, serum MBL concentration and MBL complex activity could be responsible for the different individual profiling of immune responses and could explain, at least partially, of the susceptibility to HIV-1 infection among Han Chinese population.