%0 Journal Article
%T Influenza Viral Manipulation of Sphingolipid Metabolism and Signaling to Modulate Host Defense System
%A Madhuvanthi Vijayan
%A Bumsuk Hahm
%J Scientifica
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/793815
%X Viruses attempt to create a distinctive cellular environment to favor viral replication and spread. Recent studies uncovered new functions of the sphingolipid signaling/metabolism during pathogenic virus infections. While sphingolipids such as sphingomyelin and ceramide were reported to influence the entry step of several viruses, sphingolipid-metabolizing enzymes could directly alter viral replication processes. Influenza virus was shown to increase the level of sphingosine kinase (SK) 1 to promote virus propagation. The mechanism involves regulation of intracellular signaling pathways, leading to the amplification of influenza viral RNA synthesis and nuclear export of viral ribonucleoprotein (RNP) complex. However, bovine viral diarrhea virus inhibits SK1 to enhance the efficacy of virus replication, demonstrating the presence of virus-specific strategies for modulation of the sphingolipid system. Therefore, investigating the sphingolipid metabolism and signaling in the context of virus replication could help us design innovative therapeutic approaches to improve human health. 1. Introduction Over the last twenty years, the field of sphingolipid system has received enormous attention of scientists and clinicians, since the sphingolipids have numerous important biological functions and are therapeutically applicable to the treatment of human diseases [1¨C5]. The sphingolipids are bioactive mediators and include sphingomyelin, ceramide, ceramide-1-phosphate, sphingosine, and sphingosine 1-phosphate (S1P) (Figure 1(a)). The levels of these sphingolipids are tightly regulated by cellular metabolizing enzymes to maintain normal cellular physiological conditions [6, 7]. The sphingosine analog FTY720 (fingolimod, gilenya) (Figure 1(b)) transiently represses the exit of T lymphocytes from lymph nodes and acts as an agonist of S1P receptors (S1P1 and S1P3¨C5) except for S1P receptor 2 [8, 9]. FTY720, which is a derivative of myriocin that is found in a fungus and used in Chinese medicine, is the first oral therapeutic agent approved by the US FDA to treat multiple sclerosis (MS) [10, 11]. Also, the FTY720 derivative AAL-R or S1P receptor 1 agonist was shown to alleviate influenza virus-induced immunopathology [12¨C15] and the detailed information about this is found in excellent review articles written by Oldstone and Rosen¡¯s groups [16¨C18]. Figure 1: The sphingolipid system. (a) The pathway of sphingolipid synthesis and degradation by catalytic enzymes. (b) Shown are chemical structures of the sphingolipids (ceramide, sphingosine, and S1P) and the sphingosine
%U http://www.hindawi.com/journals/scientifica/2014/793815/