Proteomics Analysis of EV71-Infected Cells Reveals the Involvement of Host Protein NEDD4L in EV71 Replication

Enterovirus 71 (EV71) is a human
enterovirus that has seriously
affected the Asia-Pacific area for the past two decades. EV71 infection
can result in mild hand-foot-and-mouth disease and herpangina and
may occasionally lead to severe neurological complications in children.
However, the specific biological processes that become altered during
EV71 infection remain unclear. To further explore host responses upon
EV71 infection, we identified proteins differentially expressed in
EV71-infected human glioblastoma SF268 cells using isobaric mass tag
(iTRAQ) labeling coupled with multidimensional liquid chromatography–mass
spectrometry (LC–MS/MS). Network analysis of proteins altered
in cells infected with EV71 revealed that the changed biological processes
are related to protein and ion transport, regulation of protein degradation,
and homeostatic processes. We confirmed that the levels of NEDD4L
and PSMF1 were increased and reduced, respectively, in EV71-infected
cells compared to mock-infected control cells. To determine the physiological
relevance of our findings, we investigated the consequences of EV71
infection in cells with NEDD4L or PSMF1 depletion. We found that the
depletion of NEDD4L significantly reduced the replication of EV71,
whereas PSMF1 knockdown enhanced EV71 replication. Collectively, our
findings provide the first evidence of proteome-wide dysregulation
by EV71 infection and suggest a novel role for the host protein NEDD4L
in the replication of this virus.