Phosphorylation of PI3K/Akt and MAPK/ERK in an early entry step of enterovirus 71

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Viruses often manipulate host cell anti-apoptotic pathways to ensure survival and replication.
• Enterovirus 71 (EV71) is a significant human pathogen, but its mechanisms for inhibiting apoptosis are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms by which EV71 subverts host cell apoptosis.
• To investigate the roles of phosphatidylinositol 3-kinase (PI3K)/Akt and MAPK/ERK signaling pathways in EV71-mediated anti-apoptotic activity.

Main Methods:

• EV71 infection of host cells.
• Analysis of key signaling pathway activation (PI3K/Akt, MAPK/ERK) and downstream targets (GSK3beta, BAD, caspase-9, FKHR) via phosphorylation.
• Use of specific pathway inhibitors.
• Experiments with UV-inactivated EV71 to differentiate early and late signaling events.

Main Results:

• EV71 infection induced early activation of both PI3K/Akt and MAPK/ERK signaling pathways.
• Activation of these pathways led to the negative regulation and phosphorylation of GSK3beta, indicating its inactivation.
• Unlike other viruses, EV71 did not phosphorylate downstream Akt targets BAD, caspase-9, or FKHR.
• UV-inactivated EV71 triggered early Akt activation but not late activation, suggesting a role for viral replication.

Conclusions:

• EV71 utilizes the phosphorylation and subsequent inactivation of GSK3beta, mediated by PI3K/Akt and MAPK/ERK pathway activation, as a mechanism to delay host cell apoptosis.
• This viral strategy likely contributes to the propagation and survival of EV71 within the host.