Fahd Al Qureshah, Jérémie Le Pen, Nicole A de Weerd, Marcela Moncada-Velez, Marie Materna, Daniel C Lin, Baptiste Milisavljevic, Fernanda Vianna, Lucy Bizien, Lazaro Lorenzo, Marc Lecuit, Jean-David Pommier, Sevgi Keles, Tayfun Ozcelik, Sigifredo Pedraza-Sanchez, Nicolas de Prost, Loubna El Zein, Hassan Hammoud, Lisa F P Ng, Rabih Halwani, Narjes Saheb Sharif-Askari, Yu Lung Lau, Anthony R Tam, Neha Singh, Sagar Bhattad, Yackov Berkun, Wasun Chantratita, Raúl Aguilar-López, Mohammad Shahrooei, Laurent Abel, Paul Bastard, Emmanuelle Jouanguy, Vivien Béziat, Peng Zhang, Charles M Rice, Aurélie Cobat, Shen-Ying Zhang, Paul J Hertzog, Jean-Laurent Casanova, Qian Zhang
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引用次数: 0
Abstract
Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses.
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