Lindesmith Lisa, Moe Christine, Marionneau Severine, Ruvoen Nathalie, Jiang Xi, Lindblad Lauren, Stewart Paul, LePendu Jacques, Baric Ralph
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Nat Med. 2003 May;9(5):548-53. doi: 10.1038/nm860. Epub 2003 Apr 14.
Infectious diseases have influenced population genetics and the evolution of the structure of the human genome in part by selecting for host susceptibility alleles that modify pathogenesis. Norovirus infection is associated with approximately 90% of epidemic non-bacterial acute gastroenteritis worldwide. Here, we show that resistance to Norwalk virus infection is multifactorial. Using a human challenge model, we showed that 29% of our study population was homozygous recessive for the alpha(1,2)fucosyltransferase gene (FUT2) in the ABH histo-blood group family and did not express the H type-1 oligosaccharide ligand required for Norwalk virus binding. The FUT2 susceptibility allele was fully penetrant against Norwalk virus infection as none of these individuals developed an infection after challenge, regardless of dose. Of the susceptible population that encoded a functional FUT2 gene, a portion was resistant to infection, suggesting that a memory immune response or some other unidentified factor also affords protection from Norwalk virus infection.
传染病通过选择修饰发病机制的宿主易感性等位基因，在一定程度上影响了群体遗传学和人类基因组结构的进化。诺如病毒感染与全球约90%的非细菌性急性肠胃炎流行有关。在此，我们表明对诺沃克病毒感染的抗性是多因素的。使用人类挑战模型，我们发现，在ABH组织血型家族中，29%的研究人群α(1,2)岩藻糖基转移酶基因（FUT2）为纯合隐性，不表达诺沃克病毒结合所需的H1型寡糖配体。FUT2易感性等位基因对诺沃克病毒感染具有完全的穿透性，因为这些个体在受到攻击后，无论剂量如何，均未发生感染。在编码功能性FUT2基因的易感人群中，一部分对感染具有抗性，这表明记忆免疫反应或其他一些未确定的因素也能提供对诺沃克病毒感染的保护。
