The role of sphingosine 1-phosphatemetabolizing enzymes in host defense to RNA virus infections
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Viruses are intracellular parasites that rely on the host cell machinery to effectively replicate themselves and spread within the host to cause disease. Thus, viruses depend on certain host proteins and signal transduction pathways for effective replication. The work here investigates the role of cellular factors of the sphingolipid system, which play an important role in the lifecycle of certain pathogenic viruses. RNA viruses such as influenza and measles are important human pathogens. Each year there are several thousands of people who get infected with influenza and measles viruses. Thus, these viruses pose a significant threat to human health. We show that, host proteins of the sphingolipid system have a significant contribution towards host defense to measles and influenza infections. Specifically, sphingosine 1-phosphate (S1P)- metabolizing enzymes namely sphingosine kinase 1 (SK1) and sphingosine 1-phosphate lyase (SPL) are involved both in virus replication and in the innate immune response to the virus infection. We have discovered that, the host protein SK1 aids measles virus replication. Therefore, measles virus hijacks this cellular protein to effectively replicate itself inside the host cells. On the other hand, the cellular protein SPL plays an antiviral role during influenza virus replication. When we increased the intracellular amounts of SPL protein, the level of influenza virus replication was decreased. Furthermore, we have studied these proteins and the pathways in molecular detail to understand how they affect virus replication and the innate immune response. Such findings are important because we can use this knowledge to target these proteins to manipulate virus replication and control the outcome of the viral infection. Eventually, we could use the knowledge to develop therapeutic strategies to combat virus infections in an effective manner. In addition to this, the current work lets us understand and appreciate the biology of virus infections to a greater extent.