Crimean-Congo hemorrhagic fever virus (CCHFV) is a virus that causes severe liver dysfunctions and hemorrhagic fever, with high mortality rate. Here, we show that CCHFV infection caused a massive lipidation of LC3 in hepatocytes. This lipidation was not dependent on ATG5, ATG7 or BECN1, and no signs for recruitment of the alternative ATG12–ATG3 pathway for lipidation was found. Both virus replication and protein synthesis were required for the lipidation of LC3. Despite an augmented transcription of SQSTM1, the amount of proteins did not show a massive and sustained increase in infected cells, indicating that degradation of SQSTM1 by macroautophagy/autophagy was still occurring. The genetic alteration of autophagy did not influence the production of CCHFV particles demonstrating that autophagy was not required for CCHFV replication. Thus, the results indicate that CCHFV multiplication imposes an overtly elevated level of LC3 mobilization that involves a possibly novel type of non-canonical lipidation.

Abbreviations: BECN1: Beclin 1; CCHF: Crimean-Congo hemorrhagic fever; CCHFV: Crimean-Congo hemorrhagic fever virus; CHX: cycloheximide; ER: endoplasmic reticulum; GFP: green fluorescent protein; GP: glycoproteins; MAP1LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; n.i.: non-infected; NP: nucleoprotein; p.i.: post-infection; SQSTM1: sequestosome 1

克里米亚-刚果出血热病毒（CCHFV）是一种导致严重肝功能障碍和出血热的病毒，死亡率很高。在这里，我们发现 CCHFV 感染导致肝细胞中 LC3 大量脂化。这种脂化不依赖于ATG5、ATG7或BECN1 ，并且没有发现招募替代 ATG12-ATG3 途径进行脂化的迹象。 LC3 的脂化需要病毒复制和蛋白质合成。尽管SQSTM1的转录增强，但受感染细胞中蛋白质的量并未显示出大量且持续的增加，这表明巨自噬/自噬对SQSTM1的降解仍在发生。自噬的遗传改变并不影响 CCHFV 颗粒的产生，这表明自噬对于 CCHFV 复制不是必需的。因此，结果表明，CCHFV 增殖导致 LC3 动员水平明显升高，这可能涉及一种新型的非典型脂化。

缩写： BECN1：Beclin 1； CCHF：克里米亚-刚果出血热； CCHFV：克里米亚-刚果出血热病毒； CHX：放线菌酮； ER：内质网； GFP：绿色荧光蛋白； GP：糖蛋白； MAP1LC3：微管相关蛋白1轻链3； MOI：感染复数； ni：未感染； NP：核蛋白； pi：感染后； SQSTM1: 隔离体 1