Autor(es): Carr Jillian M, Mahalingam Suresh, Bonder Claudine S, Pitson Stuart M

Resumo: Sphingosine kinase 1 (SphK1) is an enzyme that phosphorylates the lipid sphingosine to generate sphingosine-1-phosphate (S1P). S1P can act intracellularly as a signaling molecule - extracellularly as a receptor lig-. The SphK1/S1P axis has well-described roles in cell signaling, the cell death/survival decision, the production of a pro-inflammatory response, immunomodulation, - control of vascular integrity. Agents targeting the SphK1/S1P axis are being actively developed as therapeutics for cancer - immunological - inflammatory disorders. Control of cell death/survival - pro-inflammatory immune responses is central to the pathology of infectious disease, - we can capitalize on the knowledge provided by investigations of SphK1/S1P in cancer - immunology to assess its application to selected human infections. We have herein reviewed the growing literature relating viral infections to changes in SphK1 - S1P. SphK1 activity is reportedly increased following human cytomegalovirus - respiratory syncytial virus infections, - elevated SphK1 enhances influenza virus infection. In contrast, SphK1 activity is reduced in bovine viral diarrhea virus - dengue virus infections. Sphingosine analogs that modulate S1P receptors have proven useful in animal models in alleviating influenza virus infection but have shown no benefit in simian human immunodeficiency virus - lymphocytic choriomeningitis virus infections. We have rationalized a role for SphK1/S1P in dengue virus, chikungunya virus, - Ross River virus infections, on the basis of the biology - the pathology of these diseases. The increasing number of effective SphK1 - S1P modulating agents currently in development makes it timely to investigate these roles with the potential for developing modulators of SphK1 - S1P for novel anti-viral therapies.

Imprenta: Reviews in Medical Virology, v. 23, n. 2, p. 73-84, 2013

Identificador do objeto digital: 10.1002/rmv.1718

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Immune response ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Immune response ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue ; Chikungunya virus - Immunology

Data de publicação: 2013

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