STUDY ON RECEPTOR SPECIFICITY OF ANIMAL INFLUENZA VIRUSES

不同的流感病毒，HA的受体特异性不同：大多数禽流感病毒优先结合唾液酸-α-2，3-半乳糖(SAalpha2-3Gal)，而人类流感病毒优先结合细胞表面唾液酸寡糖上的SAalpha2，6Gal。为了了解宿主范围限制的分子基础，我们研究了唾液酸寡糖在非人类动物中流感病毒复制部位的分布。利用连锁特异性凝集素，我们发现鸭肠道和马气管衬里的上皮细胞含有SAalpha2，3Gal而不含有SAalpha2，6Gal连接，而猪气管衬里的上皮细胞同时含有SAalpha2，3Gal和SAalpha2，6Gal。接下来，我们研究了为什么突变的人HA优先识别SAalpha2，3Gal，不支持病毒在鸭肠内复制。对鸭病毒和人变异病毒受体特异性的分析表明，N-羟基唾液酸(NeuGc)的识别对…的肠道复制起重要作用鸭子体内的病毒更多。免疫组织化学检测到鸭小肠上皮细胞中有NeuGcalpha2、3的表达。这些发现表明，动物复制部位受体的存在与从动物中分离的病毒的受体特异性相对应。为了测试不同动物物种的红细胞凝集是否可以用来评估甲型流感病毒的受体特异性，我们测定了一系列病毒株的凝集活性。所有马和禽类病毒都能凝集所有动物的红细胞；被测试的物种(鸡、鸭、豚鼠、人、绵羊、山羊和奶牛)，人类病毒能凝集除马以外的所有动物的红细胞。和奶牛的红细胞。利用连接特异性凝集素对红细胞进行荧光激活的细胞分选分析表明，牛和马的红细胞都含有大量的SAalpha2，3Gal-，但在细胞表面几乎没有SAalpha2，6Gal特异的凝集素反应性寡糖，而人和鸡的红细胞含有这两种类型的寡糖。这些发现表明，与不同动物物种的红细胞的凝集试验将有助于表征甲型流感病毒的受体特异性。较少

The receptor specificity of the HA differs amongsinfluenza viruses : most avian influenza viruses preferentially bind the sialic acid-alpha-2,3-galactose (SAalpha2-3Gal) linkage, while human influenza viruses preferentially bind the SAalpha2,6Gal linkage on cell surface sialyloligosaccharides. To understand the molecular basis of host range restriction, we examined the distribution of sialyloligosaccharides at the replication site of influenza virus in nonhuman animals. Using linkage-specific lectins, we found that epitherial cells lining duck intestine and horse trachea contain SAalpha2,3Gal but not SAalpha2,6Gal linkages, whereas those lining pig trachea contain both. We next examined why the mutant human HA,which preferentially reconizes SAalpha2,3Gal, does not support virus replication in duck intestine. The analysis of the receptor specificity of duck and mutant human viruses suggested that the recognition of N-glycolyl sialic acid (NeuGc) is iportant for intestinal replication of … More virus in ducks. NeuGcalpha2,3 was immunologically detected in epitherial cells in duck uintestine. These findings show that the presence of the receptors in the replication site of animals corresponds tothe receptor specificity of viruses isolated from such animals.To test whether agglutination of erythrocytes from different animal species could be used to assess the receptor specificity of influenza A viruses, we determined the agglutinating activities of a range of virus strains. All equine and avian viruses agglutinated erythrocytes from all of the animal ; species tested (chickens, ducks, guinea pigs, humans, sheep, forses and cows), The human viruses agglutinated all but the horse. and cow erythrocytes. Fluorescene-activated cell sorting analysis of erythrocytes using linkage-specific lectins showed that both cow and horse crythrocytes contain a large amount of SAalpha2,3Gal- but virtually no SAalpha2,6Gal-specific lectin-reactive oligosaccharides on the cell surface, while human and chicken erythrocytes contain both types of oligosaccharides. These findings show that agglutinating assays with erythrocytes from different animal species would be useful in characterizing the receptor specificity of influenza A viruses. Less