Baculovirus Infection Triggers a Shift from Amino Acid Starvation-Induced Autophagy to Apoptosis

Wei Wei,Yongbo Yang,Kaiyu Liu,Yi Li,Zhongchao Gai,Jianxin Peng,Wenxian Wu,Hui Ai,Huazhu Hong,Fatah Kashanchi

doi:10.1371/journal.pone.0037457

Abstract

Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. On the other hand, many pathogens have evolved mechanisms of inhibition of autophagy such as blockage of the formation of autophagosomes or the fusion of autophagosomes with lysosomes. Baculoviruses are important insect pathogens for pest control, and autophagy activity increases significantly during insect metamorphosis. However, it is not clear whether baculovirus infection has effects on the increased autophagy. In the present study, we investigated the effects of the Autographa californica nucleopolyhedrovirus (AcMNPV) infection on autophagy in SL-HP cell line from Spodoptera litura induced under amino acid deprivation. The results revealed that AcMNPV infection did not inhibit autophagy but triggered apoptosis under starvation pressure. In the early stage of infection under starvation, mitochondrial dysfunction was detected, suggesting the organelles might be involved in cell apoptosis. The semi-quantitative PCR assay revealed that the expression of both p35 and ie-1 genes of AcMNPV had no significant difference between the starved and unstarved SL-HP cells. The western blot analysis showed that no cleavage of endogenous Atg6 occurred during the process of apoptosis in SL-HP cells. These data demonstrated that some permissive insect cells may defend baculovirus infection via apoptosis under starvation and apoptosis is independent of the cleavage of Atg6 in SL-HP cells.

Highlights

Autophagy is an essential cellular process that mediates continuous recycling of intracellular components such as organelles and protein aggregates and becomes an alternative source of energy when nutrients are scarce
We demonstrated that autophagy was induced in SL-HP cell line derived from Spodoptera litura via amino acid deprivation, which was permissive to baculovirus infection [15], the influences of baculovirus infection on the cross-talking between autophagy and apoptosis were investigated, and the possible mechanism of the shift from autophagy to apoptosis was discussed
All the four Baculoviruses replicated in SL-HP cells The infections of Autographa californica multiple nucleopolyhedrovirus (AcMNPV), Anagrapha falcifera multiple nucleopolyhedrovirus (AfMNPV), SplitMNPV and the recombinant Ac-PH-GFP-actin were tested in SL-HP cells cultured in Grace’s supplemented with 10% fetal bovine serum (FBS)

Summary

Introduction

Autophagy is an essential cellular process that mediates continuous recycling of intracellular components such as organelles and protein aggregates and becomes an alternative source of energy when nutrients are scarce. Viral subversion and inhibition of host cell autophagy have been documented for several viruses [6,7]. Some viruses have evolved mechanisms inhibiting the formation of autophagosomes or the fusion of autophagosomes with lysosomes to protect their survival and replication [8]. The baseline of autophagy is low in insect cells. Amino acid deprivation or rapamycin promoted autophagy activity in insect both in vivo and in vitro [9,10]. It is not clear whether baculovirus infection enhances autophagy in insect cells, especially under starvation pressure

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Conclusion