Association between mannose-binding lectin and HIV infection and progression in a Chinese population
Division of Serum, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, China. Molecular Immunology
(Impact Factor: 2.97).
09/2009; 47(2-3):632-8. DOI: 10.1016/j.molimm.2009.08.020
Mannose-binding lectin (MBL) is a circulating pattern recognition molecule involved in the innate immune system that mediates phagocytosis and activates complement by binding to a carbohydrate extremity. Some MBL genetic polymorphisms result in deficient protein levels and increased susceptibility to infection. The objective of this study was to investigate the association between MBL2 exon 1 polymorphisms, serum levels of normal MBL, and HIV-1 infection and progression in a Chinese population. A total of 1075 adult patients infected with HIV-1 (532 male and 543 female) were recruited. The genotype of 145 patients was determined and the genotype frequencies compared with healthy population controls. The disease status of patients was evaluated for different MBL2 genotypes and normal MBL serum levels. MBL2 exon 1 polymorphisms (A/O or O/O) were significantly more common in HIV-1-infected patients than in the healthy controls. Patients in clinical categories B/C with severe diseases were significantly more likely to have one variant allele. There was a statistical relationship between MBL2 genotypes and MBL serum levels. In addition, higher CD4(+) T cell counts and ratios of CD4(+) T cells:CD8(+) T cells were observed in patients with medium MBL levels than with low or high MBL levels. Patients with mild diseases were also more likely to have medium MBL levels than high levels. Analysis of MBL levels with respect to sex yielded differences. Median MBL levels were substantially higher in males than in females in HIV-1-infected patients. Lower CD4(+) T cell counts were detected in males with low MBL levels, but the opposite was observed in females. Our results suggest that genetic polymorphisms resulting in MBL deficiency are associated with increased susceptibility to HIV-1 infection and disease progression in the studied population. Moreover, serum circulating levels of normal MBL in HIV-1-infected patients could be an important auxiliary biological marker in association with CD4(+) T cell counts in the evaluation of HIV-1 disease progression. The sex differences in the regulation of MBL serum levels during infection merit further exploration.
Available from: Wilhelm Schwaeble
- "In humans, polymorphisms in the MBL gene are well characterized, and individuals with variant alleles have decreased serum levels (Tsutsumi et al., 2005). Low serum MBL concentrations are associated with an increased risk of disseminated disease with Neisseria meningitides (Bathum et al., 2006), and have been suggested to increase susceptibility to HIV (Tan et al., 2009), hepatitis B (Chong et al., 2005), and herpes simplex virus (Seppanen et al., 2009) infections. "
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ABSTRACT: An intact complement system is crucial for limiting West Nile virus (WNV) dissemination. Herein, we define how complement directly restricts flavivirus infection in an antibody-independent fashion. Mannose-binding lectin (MBL) recognized N-linked glycans on the structural proteins of WNV and Dengue virus (DENV), resulting in neutralization through a C3- and C4-dependent mechanism that utilized both the canonical and bypass lectin activation pathways. For WNV, neutralization occurred with virus produced in insect cells, whereas for DENV, neutralization of insect and mammalian cell-derived virus was observed. Mechanism of action studies suggested that the MBL-dependent neutralization occurred, in part, by blocking viral fusion. Experiments in mice showed an MBL-dependent accelerated intravascular clearance of DENV or a WNV mutant with two N-linked glycans on its E protein, but not with wild-type WNV. Our studies show that MBL recognizes terminal mannose-containing carbohydrates on flaviviruses, resulting in neutralization and efficient clearance in vivo.
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Available from: nature.com
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ABSTRACT: The complement system, a key component of innate immunity, is a first-line defender against foreign pathogens such as HIV-1. The role of the complement system in HIV-1 pathogenesis appears to be multifaceted. Although the complement system plays critical roles in clearing and neutralizing HIV-1 virions, it also represents a critical factor for the spread and maintenance of the virus in the infected host. In addition, complement regulators such as human CD59 present in the envelope of HIV-1 prevent complement-mediated lysis of HIV-1. Some novel approaches are proposed to combat HIV-1 infection through the enhancement of antibody-dependent complement activity against HIV-1. In this paper, we will review these diverse roles of complement in HIV-1 infection.
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