SFTS phlebovirus promotes LC3-II accumulation and nonstructural protein of SFTS phlebovirus co-localizes with autophagy proteins

Yue Sun,Xue-jie Yu,Xiao-ying Lei,Miao-miao Liu

doi:10.1038/s41598-018-23610-0

Abstract

Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly discovered tick-borne virus in the Phenuiviridae family that causes a severe hemorrhagic fever disease in East Asia. In this study we determined interactions between SFTSV and autophagy. Our results showed that LC3-II (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use of E64d and pepstatin A did not affect the expression of LC3-II protein, which indicated that the increased LC3-II may be the result of inhibition of autophagic degradation caused by SFTSV infection. However, knockdown of LC3B promotes SFTSV replication, which indicated a negative role of LC3B protein in SFTSV replication. We also detected co-localization of SFTSV non-structure (NSs) protein with LC3B, p62 and Lamp2b respectively in SFTSV infected Vero cells, which indicated the possibility of selective autophagy or chaperone-mediated autophagy involving in SFTSV infection. Our results indicated that SFTSV infection promotes LC3 accumulation and several proteins of the autophagy pathway co-localize with NSs protein during SFTSV infection.

Highlights

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever disease, which was first reported in 2010 in China and subsequently reported in South Korea and Japan[1,2,3]
Our results showed that LC3-II protein accumulated in Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) infected Vero cells compared to the mock-infected cells (Fig. 1A), which indicated that SFTSV infection might promote LC3-II synthesis or inhibit autophagic degradation
To precisely interpret the mechanism of accumulation of LC3-II by SFTSV infection, we further investigated whether E64d and pepstatin A affected LC3-II expression in SFTSV-infected Vero cells

Summary

Introduction

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever disease, which was first reported in 2010 in China and subsequently reported in South Korea and Japan[1,2,3]. The NSs proteins of various viruses from the Phenuiviridae family and other families of Bunyavirales[9] order have been reported to have important effects on interacting with host responses through different mechanisms[11]. NSs protein of Rift Valley fever virus (RVFV) forms fibrillar in the nuclei of infected cells, targets cellular TFIIH transcription factor and blocks interferon production[12,13,14,15,16]. The NSs protein of SFTSV has been reported to play essential roles in SFTSV replication and host responses[17]. The autophagosome can deliver intracellular pathogen-associated molecular patterns (PAMPs) to endosomal pattern recognition receptors (PRRs) and MHC-loading compartments to initiate innate and adaptive immune responses such as the VSV (Vesicular Stomatitis Virus) and CVB3, which deliver viral replication intermediates to TLR7 and TLR3, respectively[32,33,34]. In this study we have explored the interaction between SFTSV and autophagy in Vero cells

Methods

Results

Conclusion