Foot-and-mouth disease virus (FMDV) is the causative agent of
foot-and-mouth disease, a highly contagious, economically important
viral disease. The structural
protein VP1 plays significant roles during FMDV
infection. Here, we identified that VP1 interacted with host
ribosomal protein SA (RPSA). RPSA is a viral receptor for dengue virus and classical swine fever virus
infections. However, the incubation of susceptible cells using the anti-RPSA
antibodies did not block the
infection of FMDV. Overexpression of porcine RPSA in the insusceptible cells could not trigger FMDV
infection, suggesting that RPSA was not responsible for FMDV entry and
infection. On the contrary, we found that overexpression of RPSA suppressed FMDV replication, and knockdown of RPSA enhanced FMDV replication. We further determined that FMDV
infection activated the
mitogen-activated protein kinase (MAPK) pathway and demonstrated that MAPK pathway activation was critically important for FMDV replication. RPSA negatively regulated MAPK pathway activation during FMDV
infection and displayed an
antiviral function. FMDV VP1 interacted with RPSA to abrogate the RPSA-mediated suppressive role in MAPK pathway activation. Together, our study indicated that MAPK pathway activation was required for FMDV replication and that host RPSA played a negatively regulatory role on MAPK pathway activation to suppress FMDV replication. FMDV VP1 bound to RPSA to promote viral replication by repressing RPSA-mediated function and maintaining the activation of MAPK signal pathway.IMPORTANCE Identification of virus-cell interactions is essential for making strategies to limit virus replication and refine the models of virus replication. This study demonstrated that FMDV utilized the MAPK pathway for viral replication. The host RPSA
protein inhibited FMDV replication by suppressing the activation of the MAPK pathway during FMDV
infection. FMDV VP1 bound to RPSA to repress the RPSA-mediated regulatory effect on MAPK pathway activation. This study revealed an important implication of the MAPK pathway for FMDV
infection and identified a novel mechanism by which FMDV VP1 has evolved to interact with RPSA and maintain the activation of the MAPK pathway, elucidating new information regarding the signal reprogramming of host cells by FMDV.