Takahashi Tadanobu
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
Uirusu. 2016;66(1):101-116. doi: 10.2222/jsv.66.101.
Influenza A virus (IAV) recognizes terminal sialic acid of sialoglyco-conjugates on host cells through the viral envelope glycoprotein hemagglutinin (HA), followed by initiation of entry into the cells. Molecular species of sialic acid are largely divided into two moieties: N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). A receptor for IAV infection generally means Neu5Ac. Almost all equine IAVs and some human, swine, and duck IAVs bind not only to Neu5Ac but also to Neu5Gc. In nonhuman animals, Neu5Gc has been detected in swine and equine tracheas and the duck colon, which are the main replication sites of mammalian and avian IAVs. Therefore, Neu5Gc in these sites has been suggested to be a functional receptor for IAV infection. Humans cannot synthesize Neu5Gc due to a genetic defect of the Neu5Gc-synthesizing enzyme. We evaluated the receptor function of Neu5Gc in IAV infection in human cells. Our results indicated that Neu5Gc expression on the surface of human cells is not a functional receptor for IAV infection and that it has a negative effect on infectivity of IAV possessing Neu5Gc binding ability. IAV also binds to non-sialo 3-O-sulfated galactosylceramide (sulfatide). Sulfatide has been suggested to be a functional receptor for IAV infection. However, we have shown that sulfatide is not a functional receptor for IAV infection and that the binding of HA with sulfatide enhances progeny virus production. It is expected that functions of these glyco-molecules can be used in prevention and development of new drugs against IAV.
甲型流感病毒（IAV）通过病毒包膜糖蛋白血凝素（HA）识别宿主细胞上唾液酸糖缀合物的末端唾液酸，随后开始进入细胞。唾液酸的分子种类主要分为两部分：N-乙酰神经氨酸（Neu5Ac）和N-羟乙酰神经氨酸（Neu5Gc）。IAV感染的受体通常指Neu5Ac。几乎所有马IAV以及一些人、猪和鸭IAV不仅与Neu5Ac结合，还与Neu5Gc结合。在非人类动物中，已在猪和马的气管以及鸭的结肠中检测到Neu5Gc，这些部位是哺乳动物和禽类IAV的主要复制位点。因此，这些部位的Neu5Gc被认为是IAV感染的功能性受体。由于Neu5Gc合成酶的遗传缺陷，人类无法合成Neu5Gc。我们评估了Neu5Gc在人细胞IAV感染中的受体功能。我们的结果表明，人细胞表面的Neu5Gc表达不是IAV感染的功能性受体，并且它对具有Neu5Gc结合能力的IAV的感染性有负面影响。IAV还与非唾液酸3-O-硫酸化半乳糖神经酰胺（硫苷脂）结合。硫苷脂被认为是IAV感染的功能性受体。然而，我们已经表明硫苷脂不是IAV感染的功能性受体，并且HA与硫苷脂的结合会增加子代病毒的产生。预计这些糖分子的功能可用于IAV的预防和新药开发。
