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Open AccessArticle

Emergence of Fluoxetine-Resistant Variants during Treatment of Human Pancreatic Cell Cultures Persistently Infected with Coxsackievirus B4

Faculté de médecine, Université Lille, CHU Lille, Laboratoire de Virologie EA3610, F-59000 Lille, France
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Author to whom correspondence should be addressed.
Viruses 2019, 11(6), 486; https://doi.org/10.3390/v11060486
Received: 10 April 2019 / Revised: 16 May 2019 / Accepted: 21 May 2019 / Published: 28 May 2019
(This article belongs to the Special Issue Antiviral Agents)
This study reports the antiviral activity of the drug fluoxetine against some enteroviruses (EV). We had previously established a model of persistent coxsackievirus B4 (CVB4) infection in pancreatic cell cultures and demonstrated that fluoxetine could clear the virus from these cultures. We further report the emergence of resistant variants during the treatment with fluoxetine in this model. Four independent persistent CVB4 infections in Panc-1 cells were treated with fluoxetine. The resistance to fluoxetine was investigated in an acute infection model. The 2C region, the putative target of fluoxetine antiviral activity, was sequenced. However, Fluoxetine treatment failed to clear CVB4 in two persistent infections. The resistance to fluoxetine was later confirmed in HEp-2 cells. The decrease in viral titer was significantly lower when cells were inoculated with the virus obtained from persistently infected cultures treated with fluoxetine than those from susceptible mock-treated cultures (0.6 log TCID50/mL versus 4.2 log TCID50/mL, p < 0.0001). Some previously described mutations and additional ones within the 2C protein were found in the fluoxetine-resistant isolates. The model of persistent infection is an interesting tool for assessing the emergence of variants resistant to anti-EV molecules. The resistance of EV strains to fluoxetine and its mechanisms require further investigation. View Full-Text
Keywords: enteroviruses; coxsackievirus B4; persistent infection; fluoxetine; resistance; mutations enteroviruses; coxsackievirus B4; persistent infection; fluoxetine; resistance; mutations
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MDPI and ACS Style

Alidjinou, E.K.; Bertin, A.; Sane, F.; Caloone, D.; Engelmann, I.; Hober, D. Emergence of Fluoxetine-Resistant Variants during Treatment of Human Pancreatic Cell Cultures Persistently Infected with Coxsackievirus B4. Viruses 2019, 11, 486.

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