engleski

Antiviral activity of ribavirin against mumps virus

Mumps virus (MuV) is an important aerosol- transmitted human pathogen causing epidemic parotitis, meningitis, encephalitis, orchitis and deafness. Mumps is prevented by vaccination, although vaccine efficacy and safety are being re- examined in the last decades. Specific treatment for mumps does not exist. In our work we have treated different MuV strains with a range of concentrations of ribavirin (nucleoside analog) in two different cell lines (Vero and LLC-MK2). Dose-dependent titer decrease was present proving a strain-independent antiviral effect. Results obtained from deep sequencing show increase in population diversity for ribavirin treated virus, as well as increase in ribavirin specific mutations. We have also conducted consecutive passages of virus treated with ribavirin in different concentrations in Vero cells to determine long-term effect of mutagen on MuV. Initial decrease in titer was present after the first passage. For the lower concentrations of mutagens, titer started to rise from that point forward. Higher concentrations of ribavirin resulted in no detectable virus titer after 5 passages. We conducted three additional blind passages in the control medium that have not resulted in revival of the virus. Our results suggest that lower concentrations of ribavirin lead to mutagen resistance. We did not determine if this is a property of a whole viral population or whether it is dependent on a specific viral variant. Nonetheless, higher concentrations of ribavirin seem to cause virus extinction proposing lethal mutagenesis for mumps. This finding opens up possibilities for treatment after the infection has already taken place.

mumps virus, viral population diversity, ribavirin, antiviral activity

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