A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection. Issue 4 (13th January 2014)

• Record Type: Journal Article
• Authors: Ciencewicki, Jonathan M.; Wang, Xuting; Marzec, Jacqui; Serra, M. Elina; Bell, Douglas A.; Polack, Fernando P.; Kleeberger, Steven R.
• Is Part Of: FASEB journal. Volume 28:Issue 4(2014)
• Page Start: 1947
• Page End: 1956
• Publication Date: 2014-01-13
• Subjects: lymphoblastoid cell lines -- HapMap -- infant lung disease -- gene expression -- bronchiolitis -- MX1; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-239855
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : Respiratory syncytial virus (RSV) is the primary cause of lower respiratory tract infection during childhood and causes severe symptoms in some patients, which may cause hospitalization and death. Mechanisms for differential responses to RSV are unknown. Our objective was to develop an in vitro model of RSV infection to evaluate interindividual variation in response to RSV and identify susceptibility genes. Populations of human‐derived HapMap lymphoblastoid cell lines (LCLs) were infected with RSV. Compared with controls, RSV‐G mRNA expression varied from ~1‐ to 400‐fold between LCLs. Basal expression of a number of gene transcripts, including myxovirus (influenza virus) resistance 1 ( MX1), significantly correlated with RSV‐G expression in HapMap LCLs. Individuals in a case‐control population of RSV‐infected children who were homozygous ( n =94) or heterozygous ( n =172) for the predicted deleterious A allele in a missense G/A SNP in MX1 had significantly greater risk for developing severe RSV disease relative to those with the major allele ( n =108) (χ 2 =5.305, P =0.021; OR 1.750, 95% CI: 1.110, 2.758, P =0.021). We conclude that genetically diverse human LCLs enable identification of susceptibility genes ( e.g., MX1 ) for RSV disease severity in children, providing insight for disease risk.—Ciencewicki, J. M., Wang, X., Marzec, J., Serra, M. E., Bell, D. A., Polack, F. P., Kleeberger, S. R. A genetic model of differential susceptibility to human respiratory syncytial virus (RSV) infection. FASEB J. 28, 1947–1956 (2014). www.fasebj.org