The University of Hong Kong, China
Dr Jie ZHOU has completed her Ph.D from The University of Hong Kong. After her postdoctoral studies in UCSF, she is now a research assistant professor in Department of Microbiology, HKU.
Pandemic H1N1 2009 (H1N1pdm) influenza is commonly manifested as a mild infection but occasionally 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 comorbid 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 of CD55 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 CD55 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.
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