Stimulation of autophagy by salicylamide derivatives - implications for viral infection

Needs, Sarah; Kaas, Soren; Horne, Tony; Alonzi, Dominic and Allman, Sarah (2016). Stimulation of autophagy by salicylamide derivatives - implications for viral infection. In: Frankfurt Conference on Ubiquitin and Autophagy “Quality control in life process”, 04-07 Jul 2016, Goethe University Hospital, Frankfurt am Main, Germany.


Canonical autophagy pathways may be stimulated experimentally by a variety of means such as rapamycin treatment, endoplasmic reticulum stress or nutrient deprivation. Infection by obligate intracellular pathogens such as viruses, can serve either to trigger the induction of autophagy pathways or the suppression of autophagy within the host cell at various stages in viral biogenesis. Autophagy pathways therefore play a complex role in both anti-viral defense mechanisms and in pro-viral events, such as the promotion of viral replication and egress.

In this study, a panel of salicylamide derivates and structurally associated analogues were screened for anti-viral activity against cytopathic bovine viral diarrhoea virus (cp-BVDV), a Flaviviridae pestivirus often employed as a surrogate model of HCV due to similarities in virion structural organisation. Mardin-Darby Bovine Kidney (MDBK) cell monolayers were infected at MOI 1 with cp-BVDV. Following incubation with the virus for 6h, cell monolayers were then washed and treated for 24 h and 72h with media supplemented with each of the compounds. Viral clearance post drug treatment was quantified by immuno-fluorescence methods. Candidate drugs demonstrating anti-viral activity were identified from the panel. The effects of compounds exhibiting anti-viral activity were further examined in näive cells, and the effects on autophagy markers, ER stress markers and proteins involved in membrane trafficking pathways were quantified by immune-blotting and fluorescence assays.

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