2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 58(2024) N 2 p. 255-265; DOI 10.1134/S002689332402016X Full Text

A.N. Uvarova1*, E.A. Tkachenko2,3, E.M. Stasevich1, E.A. Bogomolova2,4, E.A. Zheremyan2,3, D.V. Kuprash1,3,4, K.V. Korneev1,5

The rs2564978(T) Allele Associated with Severe Influenza A Disrupts the Binding Site for Myeloid Differentiation Factor PU.1 and Reduces CD55/DAF Gene Promoter Activity in Macrophages

1Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
3Biological Faculty, Moscow State University, Moscow, 119234 Russia
4Department of Molecular and Biological Physics, Moscow Institute of Physics and Technology, Moscow, 141701 Russia
5National Research Center for Hematology, Ministry of Health of the Russian Federation, Moscow, 125167 Russia

Received - 2023-09-27; Revised - 2023-10-23; Accepted - 2023-10-23

The complement inhibitor CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity in influenza A infection and vascular complications in pathologies that involve excessive activation of the complement system. A luciferase reporter system was used to functionally analyze the single nucleotide polymorphism rs2564978 in the U937 human promonocytic cell line. The polymorphism is in the promoter of the CD55 gene, and its minor allele T is associated with a severe course of influenza A(H1N1)pdm09. A decreased activity of the CD55 promoter carrying the minor rs2564978(T) allele was observed in activated U937 cells, which provide a cell model of human macrophages. Using bioinformatics resources, PU.1 was identified as a potential transcription factor that may bind to the CD55 promoter at the rs2564978 site in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was verified by a PU.1 genetic knockdown with small interfering RNAs under specific monocyte activation conditions.

CD55/DAF, SNP, PU.1/SPI1, complement system