Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals

Abstract

Introduction: The present study investigated the association between mannose-binding lectin (MBL) gene polymorphism and serum levels with infection by HIV-1. Methods: Blood samples (5mL) were collected from 97 HIV-1-infected individuals resident in Belém, State of Pará, Brazil, who attended the Special Outpatient Unit for Infections and Parasitic Diseases (URE-DIPE). CD4 + T-lymphocyte count and plasma viral load were quantified. A 349bp fragment of exon 1 of the MBL was amplified via PCR, using genomic DNA extracted from controls and HIV-1-infected individuals, following established protocols. MBL plasma levels of the patients were quantified using an enzyme immunoassay kit. Results: Two alleles were observed: MBL*O, with a frequency of 26.3% in HIV-1-infected individuals; and the wild allele MBL*A (73.7%). Similar frequencies were observed in the control group (p > 0.05). Genotype frequencies were distributed according to the Hardy-Weinberg equilibrium in both groups. Mean MBL plasma levels varied by genotype, with statistically significant differences between the AA and AO (p < 0.0001), and AA and OO (p < 0.001) genotypes, but not AO and OO (p = 0.17). Additionally, CD4+ T-lymphocytes and plasma viral load levels did not differ significantly by genotype (p > 0.05). Conclusions: The results of this study do not support the hypothesis that MBL gene polymorphism or low plasma MBL concentrations might have a direct influence on HIV-1 infection, although a broader study involving a large number of patients is needed.

Role of Mannose-Binding Lectin Deficiency in HIV-1 and Schistosoma Infections in a Rural Adult Population in Zimbabwe

“…In view of available literature, we hypothesized that plasma MBL deficiency due to single locus substitutions in MBL2 resulting in varying levels of circulating MBL would have an effect on susceptibility to HIV-1 and schistosoma infections in this study population. The results of our study showed no difference in plasma MBL concentration between the HIV positive and HIV negative individuals, consistent with other reports [ 80 – 82 ]. In contrast, some have reported protective effect of normal plasma MBL levels and increased susceptibility due to low MBL levels [ 30 , 37 , 83 , 84 ], but some reported a deleterious effect of normal plasma MBL levels where high MBL levels were associated with acquiring HIV infection [ 39 ].…”

“…The reason for the differences in plasma MBL levels, MBL2 genotypes and HIV association outcomes is not clear [ 54 , 55 , 96 ] but this maybe because studies have been carried out in different populations, homosexual groups [ 37 ] and some in heterosexuals [ 30 , 38 , 91 ] and also the methods employed in these studies are different with some measuring plasma MBL levels only [ 30 , 39 , 81 , 82 , 97 , 98 ], others assessing structural alleles only [ 38 , 91 , 99 ], some looked at both [ 37 , 80 , 83 , 84 , 90 ] others in addition looked at MBL2 promoter region alleles [ 92 , 100 ]. Our study investigated all three MBL parameters, plasma MBL levels, polymorphism in the MBL2 exon 1 gene and promoter region variants.…”

Use of (alternative) coreceptors for HIV entry

“…Among north Indians, homozygosity for the codon 54-allele associated with low MBL production in exon-1 of the MBL-2 gene is associated with increased susceptibility to HIV-1 infection [89]. However, in a cohort of HIV-1-infected individuals, the MBL polymorphism was not associated with differences in viral load or CD4 þ T-cell count [90]. Lastly, MBL is expressed in the major cell types of HIV-1-infected brains, suggesting a potential association between MBL-mediated complement activation with neuroinflammation and neuronal injury in HIV-1-infected individuals [91].…”

Breaking the Glyco-Code of HIV Persistence and Immunopathogenesis

“…This soluble lectin has been shown to compete in vitro with DC-SIGN for HIV binding, thereby inhibiting DC-mediated CD4+ trans-infection [122]. However, in vivo, the association between HIV progression and MBL level/genotype remains elusive [123][124][125]. Recently, the C-type lectin L-selectin has also been described as an HIV adhesion receptor that facilitates infection of CD4+ T cells [126].…”