Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mannose-binding lectin (MBL) is an important constituent of the human innate immune system, and can bind to a wide range of pathogens, including viruses such as influenza A, HIV, herpes simplex 2, and SARS-CoV. MBL deficiency results from single nucleotide polymorphisms (SNPs) in exon 1, and the promoter region of the human MBL2 gene has been found to be associated with susceptibility to a number of infections. However, studies on the interactions between MBL and CMV infection are limited. In this study, we investigated 104 children suffering from HCMV infection, in an effort to find any association between MBL and HCMV infection of children in China. We analyzed the genotypes of 104 HCMV patients and 105 healthy controls, and investigated the distributions of polymorphisms at -550(H/L), -221(Y/X), and +4(P/Q), together with their structural variants. Although there was no significant difference in the distribution of B alleles between HCMV patients and healthy controls, the frequencies of the high-MBL-level related genotype of YA type in HCMV patients were significantly lower than those seen in healthy controls, while low-level related genotypes of XB type were more common in HCMV patients. In addition, CMV-DNA quantification revealed higher viral loads of the XB type in HCMV patients. Thus we can speculate that as an acute response protein and a pattern-recognition molecule of the innate immune system, MBL may play a role in protecting against HCMV infection in children, and MBL gene mutations may be a significant risk factor for the development of infantile HCMV infection.
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PMID:Association between mannose-binding lectin gene polymorphism and pediatric cytomegalovirus infection. 2071 77

New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.
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PMID:Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. 3277

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.
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PMID:The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury. 3322 83