Institute of Molecular Virology, ZMBE, Westfälische-Wilhelms-University, Münster, Germany.
PLoS Pathog. 2010 Sep 9;6(9):e1001099. doi: 10.1371/journal.ppat.1001099.
Influenza A viruses (IAV) bind to sialic-acids at cellular surfaces and enter cells by using endocytotic routes. There is evidence that this process does not occur constitutively but requires induction of specific cellular signals, including activation of PI3K that promotes virus internalization. This implies engagement of cellular signaling receptors during viral entry. Here, we present first indications for an interplay of IAV with receptor tyrosine kinases (RTKs). As representative RTK family-members the epidermal growth factor receptor (EGFR) and the c-Met receptor were studied. Modulation of expression or activity of both RTKs resulted in altered uptake of IAV, showing that these receptors transmit entry relevant signals upon virus binding. More detailed studies on EGFR function revealed that virus binding lead to clustering of lipid-rafts, suggesting that multivalent binding of IAV to cells induces a signaling platform leading to activation of EGFR and other RTKs that in turn facilitates IAV uptake.
甲型流感病毒 (IAV) 通过细胞内吞途径与细胞表面的唾液酸结合进入细胞。有证据表明，这个过程不是组成性发生的，而是需要诱导特定的细胞信号，包括激活促进病毒内化的 PI3K。这意味着在病毒进入过程中涉及细胞信号受体的参与。在这里，我们首次提出了 IAV 与受体酪氨酸激酶 (RTKs) 相互作用的观点。作为代表性的 RTK 家族成员，表皮生长因子受体 (EGFR) 和 c-Met 受体被研究。两种 RTK 的表达或活性的调节导致 IAV 的摄取发生改变，表明这些受体在病毒结合时传递与进入相关的信号。对 EGFR 功能的更详细研究表明，病毒结合导致脂筏的聚集，这表明 IAV 与细胞的多价结合诱导了一个信号平台，导致 EGFR 和其他 RTKs 的激活，进而促进了 IAV 的摄取。
