Flavivirus NS4A-induced Autophagy Protects Cells against Death and Enhances Virus Replication

• DOI: 10.1074/jbc.m110.192500
• Publication Date: 2011-04-22T03:01:36Z
• Authors: Jeffrey E. McLean; Aleksandra Wudzinska; Emmanuel Datan; Daniela Quaglino; Zahra Zakeri
• Keywords: Flavivirus

Flaviviruses include the most prevalent and medically challenging viruses. Persistent infection with flaviviruses of epithelial cells hepatocytes that do not undergo cell death is common. Here, we report that, in cells, up-regulation autophagy following flavivirus markedly enhances virus replication one gene, NS4A, uniquely determines autophagy. Dengue-2 Modoc (a murine flavivirus) kill primary macrophages but protect fibroblasts against provoked by several insults. The flavivirus-induced protection derives from autophagy, as starvation or inactivation mammalian target rapamycin also protects insult, whereas inhibition via PI3K nullifies conferred flavivirus. Inhibition limits both cells. Expression NS4A sufficient to induce PI3K-dependent death; expression other viral genes, including NS2A NS4B, fails stressors. Flavivirus protein induces thus them during infection. As vital these therefore identified a critical determinant replication.