Review
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World J Biol Chem. May 26, 2014; 5(2): 93-105
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.93
Regulation of cell survival and death during Flavivirus infections
Sounak Ghosh Roy, Beata Sadigh, Emmanuel Datan, Richard A Lockshin, Zahra Zakeri
Sounak Ghosh Roy, Beata Sadigh, Emmanuel Datan, Richard A Lockshin, Zahra Zakeri, Department of Biology, Queens College and Graduate Center of the City University of New York, Queens, New York, NY 11367, United States
Author contributions: Sadigh B and Datan E contributed equally to this paper; all the authors participated in the paper.
Supported by NIAID NIH grant to Zakeri Z, No. 1R15AIO94351-01; the NIH NIGMS (MARC-USTAR), No. T 34 GM070387
Correspondence to: Zahra Zakeri, PhD, Department of Biology, Queens College and Graduate Center of the City University of New York, 65-30 Kissena Blvd, Queens, New York, NY 11367, United States. zahra_zakeri@hotmail.com
Telephone: +1-718-9973417 Fax: + 1-718-9973429
Received: December 17, 2013
Revised: February 27, 2014
Accepted: April 25, 2014
Published online: May 26, 2014
Processing time: 190 Days and 4.4 Hours
Abstract

Flaviviruses, ss(+) RNA viruses, include many of mankind’s most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic (Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause.

Keywords: Flavivirus; Dengue virus; West Nile virus; Japanese encephalitis virus; Programmed cell death; Apoptosis; Extrinsic pathway; Intrinsic pathway; Autophagy; Necrosis

Core tip: The pathogenicity of Flaviviruses derives from their ability to infect many types of cells. They can activate both intrinsic and extrinsic pathways of apoptosis, by many means. Dengue and Japanese encephalitis virus can also activate autophagy, whereby autophagy temporarily spares the infected cell, allowing longer reproduction of virus and protecting the cell against other stresses. Given the versatility of these viruses, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause.