HSC70, HSPA1A, and HSP90AB1 Facilitate Ebola Virus trVLPs to Induce Autophagy

Abstract

ABSTRACTEbola virus (EBOV) can induce autophagy to benefit the virus life cycle, but detailed mechanisms remain to be elucidated. We previously found that EBOV GP and VP40 proteins interact with HSC70 (HSPA8), HSPA1A, and HSP90AB1. Thus, we presumed that EBOV likely induced autophagy by virus protein-host HSC70 or co-chaperon interactions via chaperone-mediated autophagy (CMA). We developed EBOV-trVLPs to model the EBOV life cycle, infected 293T cells with trVLPs, evaluated CMA by GFP-LC3 and RFP-LAMP1 co-localization, transmission electron microscopy (TEM) observation, and immunoblot analysis. The results demonstrated that EBOV-trVLPs induce autophagy which could not be inhibited by 3-MA significantly; autophagosomes and autolysosomes are obviously in the cytoplasm confirming CMA in cells infected with trVLPs. Meanwhile, a knockdown of HSC70 and relevant co-chaperones could inhibit trVLPs-associated autophagy, but no effort to Akt/mTOR/PHLPP1 pathway. These data indicate that EBOV-trVLPs could induce autophagy by CMA but was not limited by the CMA pathway. HSC70, HSPA1A, and HSP90AB1 participate and regulate CMA induced by EBOV-trVLPs. This was the first study about EBOV-trVLPs-induction of CMA and provides insight into the viral protein-host protein interaction, which is probably associated with CMA.HighlightsEBOV-trVLPs induce chaperone-mediated autophagy (CMA) but are not limit by CMA.HSC70, HSPA1A, and HSP90AB1 facilitate EBOV-trVLPs to induce autophagyKnockdown of HSC70, HSPA1A, and HSP90AB1 inhibit EBOV-trVLPs-induced CMA.