Journal of Virology · 2012 · 60 citations · 33 references
Life SciencesInfectious DiseasesMolecular BiologyImmunopathologyMolecular VirologyVirologyAntiviral TherapyViral Hemorrhagic FeversViral InfectionsViral PathogenesisViral PathologyVirus-host InteractionsAntiviral Signaling PathwaysLymphocytic ChoriomeningitisPhosphatidylinositol 3-Kinase PathwayPi3k InhibitorsPi3k SignalingPi3k-akt Signaling PathwayViral Rna SynthesisViral Therapeutic Targets
Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever (HF) disease in humans and pose a significant public health concern in regions where they are endemic. On the other hand, evidence indicates that the globally distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway participates in many cellular processes, including cell survival and differentiation, and also has been shown to play important roles in different steps of the life cycles of a variety of viruses. Here we report that the inhibition of the PI3K/Akt pathway inhibited budding and to a lesser extent RNA synthesis, but not cell entry, of LCMV. Accordingly, BEZ-235, a PI3K inhibitor currently in cancer clinical trials, inhibited LCMV multiplication in cultured cells. These findings, together with those previously reported for Junin virus (JUNV), indicate that targeting the PI3K/Akt pathway could represent a novel antiviral strategy to combat human-pathogenic arenaviruses.
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Phosphatidylinositol 3-Kinase Encoded by Yeast <i>VPS</i> 34 Gene Essential for Protein Sorting
Peter Schu, Kaoru Takegawa, Michael Fry et al. · Science · 1993 · 921 citations