Baculovirus IAP1 induces caspase-dependent apoptosis in insect cells

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Baculoviruses encode inhibitors of apoptosis (IAPs) in five groups (IAP1-5).
• While IAP3s are known to be anti-apoptotic, the functions of other IAP groups during viral infection remain unclear.
• Previous work showed Hyphantria cunea multiple nucleopolyhedrovirus (HycuMNPV) Hycu-IAP3 has anti-apoptotic activity, but Hycu-IAP1's role was unknown.

Purpose of the Study:

• To investigate the functional roles of baculovirus IAP1 proteins.
• To determine if baculovirus IAP1s can induce apoptosis.
• To elucidate the mechanism by which Hycu-IAP1 affects apoptosis and caspase activity.

Main Methods:

• Transient expression assays in various lepidopteran and dipteran cell lines.
• Apoptosis induction assays and caspase-3-like protease activity measurements.
• RNA interference (RNAi) to silence hycu-iap1 expression.
• Western blot analysis to detect caspase cleavage.

Main Results:

• Transient expression of Hycu-IAP1 induced apoptosis and stimulated caspase-3-like protease activity in multiple cell lines.
• IAP1s from other baculoviruses (AcMNPV, BmNPV, OpMNPV) also induced apoptosis.
• Hycu-IAP1-induced apoptosis was inhibited by the anti-apoptotic Hycu-IAP3.
• Caspase-3-like protease activity was stimulated late in HycuMNPV and OpMNPV infections.
• Silencing hycu-iap1 repressed caspase activity in HycuMNPV-infected cells.
• Initiator caspase Bm-Dronc was cleaved upon transfection with Hycu-IAP1.

Conclusions:

• Baculovirus IAP1s are capable of inducing caspase-dependent apoptosis.
• This pro-apoptotic function of IAP1s may involve the displacement of cellular IAPs that normally inhibit initiator caspase activation.
• These findings reveal a novel role for baculovirus IAP1s in promoting viral infection through programmed cell death induction.