All blots and microscopy images

Over the years, mounting evidence has been demonstrated that lipid reprogramming is a central strategy that enterovirus 71 (EV71) employs to ensure efficient replication and pathogenesis. By manipulating host cell lipid metabolism, the virus creates an optimal environment for its survival and spread.Recently, emerging research suggests Lipoprotein a (Lp(a)) may also play a role in viral infections, including virus replication. However, the crosstalk between Lp(a)and EV71 replication remains to be illustrated. In this study, we firstly found that EV71 infection up-regulated intracellular Lp(a) levels. Next, we provided strong novel evidence that intracellular Lp(a) can activate p38 MAPK signaling pathway, which induces autophagy to facilitate EV71 replication. Moreover, our data indicate that active p38 MAPK signaling pathway can increase the expression levels of Lp(a) receptors. Collectively, our study demonstratesthat EV71 infection can enhance higher intracellular levels of Lp(a), which in turn results in promoting EV71 replication. Targeting these Lp(a)-related pathways may offer a promising avenue for developing novel antiviral therapies to combat EV71 infection, especially given the absence of specific antiviral drugs for this virus.