Steinhauer D A
National Institute for Medical Research, The Ridgeway, London, Mill Hill, NW7 1AA, United Kingdom.
Virology. 1999 May 25;258(1):1-20. doi: 10.1006/viro.1999.9716.
Although human epidemics of influenza occur on nearly an annual basis and result in a significant number of "excess deaths," the viruses responsible are not generally considered highly pathogenic. On occasion, however, an outbreak occurs that demonstrates the potential lethality of influenza viruses. The human pandemic of 1918 spread worldwide and killed millions, and the limited human outbreak of highly pathogenic avian viruses in Hong Kong at the end of 1997 is a warning that this could happen again. In avian species such as chickens and turkeys, several outbreaks of highly pathogenic influenza viruses have been documented. Although the reason for the lethality of the human 1918 viruses remains unclear, the pathogenicity of the avian viruses, including those that caused the human 1997 outbreak, relates primarily to properties of the hemagglutinin glycoprotein (HA). Cleavage of the HA precursor molecule HA0 is required to activate virus infectivity, and the distribution of activating proteases in the host is one of the determinants of tropism and, as such, pathogenicity. The HAs of mammalian and nonpathogenic avian viruses are cleaved extracellularly, which limits their spread in hosts to tissues where the appropriate proteases are encountered. On the other hand, the HAs of pathogenic viruses are cleaved intracellularly by ubiquitously occurring proteases and therefore have the capacity to infect various cell types and cause systemic infections. The x-ray crystal structure of HA0 has been solved recently and shows that the cleavage site forms a loop that extends from the surface of the molecule, and it is the composition and structure of the cleavage loop region that dictate the range of proteases that can potentially activate infectivity. Here influenza virus pathogenicity is discussed, with an emphasis on the role of HA0 cleavage as a determining factor.
尽管人类流感几乎每年都会爆发，并导致大量“超额死亡”，但引发这些疫情的病毒通常不被认为具有高致病性。然而，偶尔也会爆发一些疫情，显示出流感病毒的潜在致死性。1918年的全球大流行造成数百万人死亡，而1997年底在香港发生的高致病性禽流感病毒在人类中的小规模爆发则警示人们，这种情况可能再次发生。在鸡和火鸡等禽类中，已经记录了几起高致病性流感病毒的爆发。虽然1918年人类流感病毒致死的原因尚不清楚，但包括导致1997年人类疫情的那些禽流感病毒的致病性，主要与血凝素糖蛋白（HA）的特性有关。HA前体分子HA0的切割是激活病毒感染性所必需的，宿主中激活蛋白酶的分布是决定病毒嗜性以及致病性的因素之一。哺乳动物和非致病性禽流感病毒的HA在细胞外被切割，这限制了它们在宿主中的传播，只能在遇到合适蛋白酶的组织中传播。另一方面，致病性病毒的HA在细胞内被普遍存在的蛋白酶切割，因此有能力感染各种细胞类型并引起全身感染。HA0的X射线晶体结构最近已被解析，结果显示切割位点形成一个从分子表面延伸出来的环，正是切割环区域的组成和结构决定了可能激活感染性的蛋白酶范围。本文将讨论流感病毒的致病性，重点是HA0切割作为决定因素的作用。
