CD55 Genetic Variations Increase The Disease Severity Of Pandemic H1N1 (2009) Influenza Infection | 17900
Epidemiology: Open Access
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andemic H1N1 2009 (H1N1pdm) influenza is commonly manifested as a mild infection but occasionally treated as a
severe pneumonia. Unlike seasonal influenza, people under 65 years of age were infected preferentially, with high rate of
severe infection and mortality in younger patients globally and in Hong Kong. Among these patients, about one third of the
severe and fatal cases do not have co-morbid conditions, implicating that inter-individual genetic variation may account for
the distinct disease severity of H1N1pdm infection. An initial small scale genome wide association study guided the selection
single nucleotide polymorphisms in 425 Chinese patients with severe (n=177) and mild (n=248) disease. Carriers
of rs2564978 genotype T/T were significantly associated with severe infection (OR 1.75, p=0.011) after adjusting the clinical
confounders. Allele-specific effect on
expression was examined and ascribed to a promoter indel variation rs3841376,
which was in perfect linkage disequilibrium with rs2564978. The promoter variant with deletion exhibited significantly lower
transcriptional activity. We further demonstrated that CD55 can protect respiratory epithelial cells from complement attack.
We also demonstrated that CD55 knockout mice are more susceptible to lethal infection of H1N1pdm. In conclusion, CD55
gene polymorphisms are associated with severe H1N1pdm infection. CD55 may exert a substantial impact on the disease
severity of H1N1pdm infection.
Jie Zhou has completed her PhD from The University of Hong Kong. After her Postdoctoral studies in UCSF, USA she is now a Research Assistant Professor in
Department of Microbiology at Hong Kong University.
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