A functional variation in CD55 increases the severity of 2009 pandemic H1N1 influenza A virus infection.
Infection due to 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized that host genetic variations may contribute to disease severity. An initially small-scale genome-wide association study guided the selection of CD55 single-nucleotide polymorphisms in 425 Chinese patients with severe (n = 177) or mild (n = 248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (odds ratio, 1.75; P = .011) under a recessive model, after adjustment for clinical confounders. An allele-specific effect on CD55 expression was revealed and ascribed to a promoter indel variation, which was in complete 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. Additionally, A(H1N1)pdm09 infection promoted CD55 expression. In conclusion, CD55 polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A(H1N1)pdm09 infection.
Department of Microbiology, The University of Hong Kong, Queen Mary Hospital, Pokfulam Rd, Pokfulam, Hong Kong Special Administrative Region, China.
Jie
J
Zhou
Kelvin Kai-Wang
KK
To
Hui
H
Dong
Zhong-Shan
ZS
Cheng
Candy Choi-Yi
CC
Lau
Vincent K M
VK
Poon
Yan-Hui
YH
Fan
You-Qiang
YQ
Song
Herman
H
Tse
Kwok-Hung
KH
Chan
Bo-Jian
BJ
Zheng
Guo-Ping
GP
Zhao
Kwok-Yung
KY
Yuen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018958:CD55 Antigens / Q000235:genetics* / Q000276:immunology; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D055815:Young Adult
D018958:CD55 Antigens