Matrosovich M N, Gambaryan A S, Teneberg S, Piskarev V E, Yamnikova S S, Lvov D K, Robertson J S, Karlsson K A
M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow, Russia.
Virology. 1997 Jun 23;233(1):224-34. doi: 10.1006/viro.1997.8580.
Avian influenza virus strains representing most hemagglutinin (HA) subtypes were compared with human influenza A (H1N1,H3N2) and B virus isolates, including those with no history of passaging in embryonated hen's eggs, for their ability to bind free N-acetylneuraminic acid (Neu5Ac) and sialylollgosaccharides in a competitive binding assay and to attach to gangliosides in a solid-phase adsorption assay. The avian viruses, irrespective of their HA subtype, showed a higher affinity for sialyl-3-lactose and the other Neu5Ac2-3Gal-terminated oligosaccharides and a lower affinity for sialyl-6-lactose than for free Neu5Ac, indicative of specific interactions between the HA and the 3-linked Gal and poor accommodation of 6-linked Gal in the avian receptor-binding site (RBS). Human H1 and H3 strains, by contrast, were unable to bind to 3-linked Gal, interacting instead with the asialic portion of sialyl-6-(N-acetyllactosamine). Different parts of this moiety were recognized by H3 and H1 subtype viruses (Gal and GlcNAc, respectively). Comparison of the HA amino acid sequences revealed that residues in positions. 138, 190, 194, 225, 226, and 228 are conserved in the avian RBS, while the human HAs harbor substitutions at these positions. A characteristic feature of avian viruses was their binding to Neu5Ac2-3Gal-containing gangliosides. This property of avian precursor viruses was preserved in early human H3 isolates, but was gradually lost with further circulation of the H3 HA in humans. Consequently, later human H3 isolates, as well as H1 and type B human strains, were unable to bind to short Neu5Ac2-3Gal-terminated gangliosides, an incompatibility that correlated with higher glycosylation of the HA globular head of human viruses. Our results suggest that the RBS is highly conserved among HA subtypes of avian influenza virus, while that of human viruses displays distinctive genotypic and phenotypic variability.
在竞争性结合试验中，将代表大多数血凝素（HA）亚型的禽流感病毒株与甲型（H1N1、H3N2）和乙型人流感病毒分离株进行比较，这些人流感病毒分离株包括那些没有在鸡胚中传代历史的毒株，比较它们结合游离N - 乙酰神经氨酸（Neu5Ac）和唾液酸寡糖的能力，以及在固相吸附试验中与神经节苷脂结合的能力。无论HA亚型如何，禽流感病毒对唾液酸 - 3 - 乳糖和其他Neu5Ac2 - 3Gal末端寡糖显示出更高的亲和力，对唾液酸 - 6 - 乳糖的亲和力低于对游离Neu5Ac的亲和力，这表明HA与3 - 连接的半乳糖之间存在特异性相互作用，且禽流感病毒受体结合位点（RBS）对6 - 连接的半乳糖容纳性较差。相比之下，人H1和H3毒株无法与3 - 连接的半乳糖结合，而是与唾液酸 - 6 - （N - 乙酰乳糖胺）的去唾液酸部分相互作用。H3和H1亚型病毒分别识别该部分的不同部分（半乳糖和N - 乙酰葡糖胺）。HA氨基酸序列的比较显示，138、190、194、225、226和228位的残基在禽流感病毒的RBS中保守，而人HA在这些位置存在替换。禽流感病毒的一个特征是它们与含Neu5Ac2 - 3Gal的神经节苷脂结合。禽流感前体病毒的这一特性在早期人H3分离株中得以保留，但随着H3 HA在人群中的进一步传播而逐渐丧失。因此，后来的人H3分离株以及H1和乙型人毒株无法与短的Neu5Ac2 - 3Gal末端神经节苷脂结合，这种不相容性与人病毒HA球状头部更高的糖基化相关。我们的结果表明，RBS在禽流感病毒的HA亚型中高度保守，而人病毒的RBS则表现出独特的基因型和表型变异性。
