title: The PI3K/Akt pathway contributes to arenavirus budding.
abstract: 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.
authors.affiliation: Department of Immunology and Microbial Science IMM-6, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Urata
authors.forename: Nhi
authors.initials: N
authors.lastname: Ngo
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
mesh_terms: D000818:Animals; D018050:Arenavirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002867:Chromones / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007836:Lassa virus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects; D057074:Virus Release / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D002867:Chromones; D007093:Imidazoles; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D011804:Quinolines; D012367:RNA, Viral; D020123:Sirolimus; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C531198:dactolisib