Autophagy during early stages contributes to bovine viral diarrhea virus replication in MDBK cells
Autophagy during early stages contributes to bovine viral diarrhea virus replication in MDBK cells
复制标题
早期自噬有助于牛病毒性腹泻病毒在 MDBK 细胞中的复制
DOI：
10.1002/jobm.201300750
复制
发表时间：
2014-10-01
影响因子：
3.1
通讯作者：
Chen, Chuangfu
中科院分区：
文献类型：
--
作者：
Fu, Qiang;Shi, Huijun;Chen, Chuangfu
自噬（或自噬作用）是细胞在营养耗竭、外源病原体或其他刺激下降解细胞质中不需要或功能失调的细胞成分或细胞器的基本和精确的控制过程。这一过程通过溶酶体依赖的机制导致受损或多余的细胞器和大分子复合物的去除。牛病毒性腹泻病毒（BVDV）是黄病毒科（鼠疫病毒属）的一种ssRNA病毒。由于牛的繁殖性能和小牛生产性能差，BVDV感染会造成重大的经济损失。在我们之前的研究中，我们已经证明BVDV NADL感染显著增加MDBK细胞的自噬。为了进一步明确自噬与BVDV感染之间的相互作用，我们研究了自噬对BVDV NADL复制的影响。结果表明，3-甲基腺嘌呤（3-MA）或wortmannin可抑制BVDV自噬，慢病毒介导的RNA干扰（RNAi）可抑制LC3和Beclin1的表达，抑制BVDV NADL的复制。相比之下，研究结果表明，自噬诱导剂雷帕霉素在感染后18h （pi）内显著增加了BVDV NADL的复制。然而，BVDV NADL 5UTRs的mRNA水平在18h后呈下降趋势，氯喹处理逆转了这一作用。因此，我们推断感染BVDV NADL会增加自噬，这反过来又有利于BVDV NADL在早期阶段的复制。
Autophagy (or autophagocytosis) is an essential and precise control process by which cells degrade unnecessary or dysfunctional cellular components or organelles in the cytoplasm in response to nutrient depletion, exogenous pathogens, or other stimuli. This process results in the removal of damaged or surplus organelles and macromolecular complexes via a lysosome-dependent mechanism. Bovine viral diarrhea virus (BVDV) is a ssRNA virus of the Flaviviridae family (genus Pestivirus). BVDV infection results in major economic losses due to poor reproductive performance and poor calf performance in cattle herds. In our previous studies, we have shown that BVDV NADL infection significantly increases autophagy in MDBK cells. To further define the interactions between autophagy and BVDV infection, we investigated the effects of autophagy on the replication of BVDV NADL. The findings showed that autophagy was inhibited by treatment with 3-methyladenine (3-MA) or wortmannin and that the knockdown of LC3 and Beclin1 using lentivirus-mediated RNA interference (RNAi) suppressed BVDV NADL replication. In contrast, the findings showed the replication of BVDV NADL was significantly increased by treatment with the autophagy inducer rapamycin within 18h post-infection (pi). However, the mRNA levels of BVDV NADL 5UTRs showed a downward trend after 18h pi, and this effect was reversed by chloroquine treatment. Therefore, we inferred that infection with BVDV NADL increases autophagy, which in turn favors BVDV NADL replication at early stages.