Measuring the effect of Ribavirin on Crimean-CongoHemorrhagic Fever Virus(CCHFV)

Background and Aim : Aim: The effect of ribavirin treatment on viral populations by deepsequencing analysis of plasma samples obtained from a CCHFV infected patient before, during,and after a ۵ day regimen of ribavirin treatment. Background: Crimean Congo hemorrhagic fevervirus (CCHFV) is a tick borne virus(Ixodidae family) that causes Crimean Congo hemorrhagicfever. CCHFV is a negative stranded, segmented RNA . In the genus Orthonairovirus ,familyNairoviridae. Treatment options for patients are limited. Ribavirin has also been used for treatmentand prophylaxis, although its efficacy remains controversial.Methods : Five days into the course of infection, the patient received ۱۰۰۰ mg of ribavirin orallyevery ۶ hours for ۲۴ hours and intravenously for the next ۲۴ hours, followed by ۵۰۰ mg ofintravenous ribavirin every ۸ hours for ۴ days, in addition to supportive care . Plasma sampleswere collected during the course of treatment and used for deep sequencing and genomic analyses.Viral loads were measured by quantitative RT PCR analysis.Results : To define the type of mutations occurring in each sample during and after ribavirintreatment, the frequency of indels and transversions was measured over time .Transversionsincreased between day ۲ and day ۳ of ribavirin treatment. The nucleotide diversity furtherincreased by day ۶ after the cessation of treatment and plateaued in the subsequent days. The indelfrequency increased dramatically between days ۲ and ۳ of ribavirin treatment and remained highuntil day ۸.Conclusion : The CCHFV load dropped during ribavirin treatment and subclonal diversity(transitions) and indels increased in viral genomes during treatment.These data demonstrate themutagenic effect of ribavirin on CCHFV in vivo.Studies measuring the mutational effect ofribavirin on viral populations have identified an increase in G to A and C to T transitions. Despitethese findings, systematic reviews of studies measuring the effect of ribavirin on CCHFV infectedpatient outcomes have been incomplete or inconclusive, leading the field to doubt ribavirin’sefficacy for human treatment.

کلیدواژه ها:

Crimean–Congo hemorrhagic fever virus ، Ribavirin ، Treatment ، mutational