Abstract
BackgroundHost genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. The aim of this study was to estimate the frequency of alleles, genotypes and haplotypes related to -550, -221 and exon 1 polymorphisms of the MBL2 gene and investigate their association with HHV-8 in people living with HIV/AIDS (PLWHA), as well as the impacts on CD4 cell count and HIV viral load in HIV/HHV-8 coinfected and HIV monoinfected patients.ResultsA cross sectional study in PLWHA, with and without HHV-8 infection, exploring associations between different factors, was performed in the outpatient infectious and parasitic diseases clinic at a referral hospital. Genomic DNA extractions from leukocytes were performed using a commercial Wizard®Genomic DNA Purification kit (Promega, Madison, WI). The promoter region (-550 and -221) was genotyped with the TaqMan system (Applied TaqMan Biosystems® genotyping Assays), and the structural region (exon1) was genotyped with Express Sybr Greener Supermix kit (Invitrogen, USA). In total, 124 HIV/HHV-8 coinfected and 213 HIV monoinfected patients were analysed. Median TCD4 counts were significantly lower in HIV/HHV-8 coinfected patients, whereas the mean of the first and last viral load of HIV did not present significant difference. There was no difference in frequency between the LL, YY and AA genotypes between the HIV/HHV-8 coinfected or HIV monoinfected patients. However, in a multivariate analysis, coinfected patients with the intermediate expression haplotype of the MBL2 gene had an odds ratio of 3.1-fold (CI = 1.2–7.6) of their last CD4 cell count being below 350 cells/mm3. Among the coinfected individuals, four developed KS and presented the intermediate expression MBL haplotype, with three being HYA/LXA and one being LYA/LYO.ConclusionsHost genetic factors, such as -550, -221 and exon 1 polymorphisms, can be related to the may modify coinfections and/or to the development clinical manifestations caused by HHV-8, especially in HIV/HHV-8 coinfected patients who present the intermediate expression haplotypes of MBL.
Highlights
Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of Mannose-binding lectin (MBL) protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections
The prevalence of Human herpesvirus 8 (HHV-8) varies according to geographic regions and sub-populations, but after the human immunodeficiency virus (HIV) epidemic, the incidence of Kaposi’s sarcoma (KS) increased drastically compared to HIV-negative individuals, being one of the commonest cancers in people living with HIV (PLWHA) [3,4,5,6]
Mannose-binding lectin (MBL) is a protein of the innate immune system that binds with high affinity to mannose or other carbohydrates that may be present on the surface of the pathogens
Summary
Host genetic factors such as MBL2 gene polymorphisms cause defects in the polymerization of MBL protein and result in a functional deficiency and/or in low serum levels that can influence susceptibility to various viral infections. Human herpesvirus 8 (HHV-8) is associated with all forms of Kaposi’s sarcoma (KS), being the necessary aetiological agent but insufficient alone for the development of this disease [1, 2] Other factors such as host genetic polymorphisms may influence the development of clinical manifestations caused by HHV8. The prevalence of HHV-8 varies according to geographic regions and sub-populations, but after the human immunodeficiency virus (HIV) epidemic, the incidence of KS increased drastically compared to HIV-negative individuals, being one of the commonest cancers in people living with HIV (PLWHA) [3,4,5,6] These coinfected patients have a more aggressive clinical course and progression to death [3,4,5,6]. MBL can mediate phagocytosis by macrophages, and when associated with serine protease (MASP), it activates the complement system by the lectin pathway in an antibody-independent mechanism [10, 11]
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