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Functional variants of MARCO modulate susceptibility to respiratory syncytial virus (RSV)
Author(s) -
Marzec Jacqui M,
Ciencewicki Jon M,
Kleeberger Steven R
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.550.3
Subject(s) - single nucleotide polymorphism , biology , allele , snp , genetics , transfection , microbiology and biotechnology , pathogenesis , gene , genotype , immunology
MARCO (macrophage associated receptor of collagenous structure) is a scavenger receptor that recognizes specific pathogens such as endotoxin and viral particles. We previously identified MARCO variants that associate with susceptibility to RSV disease, however the mechanism is unclear. We sought to identify functional variations in MARCO that modulate pathogenesis of RSV‐induced lower respiratory tract disease. The MARCO promoter was sequenced and aligned to identify variant single nucleotide polymorphisms (SNPs). Deletion constructs and MARCO polymorphic variants were amplified from genomic DNA and cloned into a pGL3 vector, transfected into A549 and Beas2B cells, and basal and RSV‐inducible MARCO activity assessed. We used gel shift analysis for binding efficiency and confirmation of transcription factor binding sites. One novel SNP within the MARCO promoter associated with RSV susceptibility in vitro , and another was located in a putative ARE site. We found a significant reduction in baseline transcriptional activity with the ‐ 1118A allele and the ‐156G allele. Similar results were found for transiently transfected cells exposed to RSV. Overall binding efficiency was reduced with the ‐156C allele, however NRF2:MARCO binding was enhanced. We conclude that functional SNPs in MARCO modulate RSV susceptibility. Support: NIEHS Division of Intramural Research.