Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells
Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells
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DOI：
10.1128/jvi.02827-06
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发表时间：
2007-05-01
影响因子：
5.4
通讯作者：
Perez, Daniel R.
中科院分区：
文献类型：
--
作者：
Wan, Hongquan;Perez, Daniel R.
H9N2 亚型甲型流感病毒在许多欧亚国家的家禽中流行，偶尔会引起人类临床呼吸道疾病。虽然一些禽类 H9N2 病毒在血凝素 (HA) 受体结合位点的第 226 位氨基酸处具有谷氨酰胺 (Q)，但越来越多的分离株在该位置具有亮氨酸 (L)，这与人类 H2 和 H3 亚型病毒的稳定谱系的建立有关。人们对这种分子特征在 H9N2 病毒感染人类中的重要性知之甚少。我们在此表明，在体外培养的人气道上皮（HAE）细胞的单周期感染过程中，含有L-226的H9N2病毒表现出人类病毒样细胞向性（优先感染非纤毛细胞），这与含有Q-226的H9N2分离株（以1:1至3:2的比例感染纤毛细胞和非纤毛细胞）或其他病毒所表现出的向性不同。水禽病毒（优先感染纤毛细胞）。在 HAE 培养物中的多个复制周期中，含有 L-226 的 H9N2 分离株持续更有效地生长，并达到比含有 Q-226 的菌株高约 100 倍的峰值滴度，尽管峰值滴度显着低于人类 H3N2 病毒诱导的峰值滴度。我们的结果表明，RA 中残基 226 的变异会影响 H9N2 病毒在 HAE 细胞中的细胞趋向性和复制，并可能对这些病毒感染人类的能力产生影响。
Influenza A viruses of the H9N2 subtype are endemic in poultry in many Eurasian countries and have occasionally caused clinical respiratory diseases in humans. While some avian H9N2 viruses have glutamine (Q) at amino acid position 226 of the hemagglutinin (HA) receptor-binding site, an increasing number of isolates have leucine (L) at this position, which has been associated with the establishment of stable lineages of the H2 and H3 subtypes of viruses in humans. Little is known about the importance of this molecular trait in the infection of H9N2 viruses in humans. We show here that during the course of a single cycle of infection in human airway epithelial (HAE) cells cultured in vitro, the L-226-containing H9N2 viruses displayed human virus-like cell tropisms (preferentially infecting nonciliated cells) different from the tropisms showed by Q-226-containing H9N2 isolates (which infect both ciliated and nonciliated cells at ratios of 1:1 to 3:2) or other waterfowl viruses (which preferentially infect ciliated cells). During multiple cycles of replication in HAE cultures, L-226-containing H9N2 isolates grew consistently more efficiently and reached approximately 100-fold-higher peak titers than those containing Q-226, although peak titers were significantly lower than those induced by human H3N2 viruses. Our results suggest that the variation in residue 226 in the RA affects both cell tropism and replication of H9N2 viruses in HAE cells and may have implications for the abilities of these viruses to infect humans.