favipiravir and Flavivirus-Infections

Chronic viral disease constitutes a major global health problem, with several hundred million people affected and an associated elevated number of deaths. An increasing number of disorders caused by human flaviviruses are related to their capacity to establish a persistent infection. Here we show that Usutu virus (USUV), an emerging zoonotic flavivirus linked to sporadic neurologic disease in humans, can establish a persistent infection in cell culture. Two independent lineages of Vero cells surviving USUV lytic infection were cultured over 82 days (41 cell transfers) without any apparent cytopathology crisis associated. We found elevated titers in the supernatant of these cells, with modest fluctuations during passages but no overall tendency towards increased or decreased infectivity. In addition to full-length genomes, viral RNA isolated from these cells at passage 40 revealed the presence of defective genomes, containing different deletions at the 5' end. These truncated transcripts were all predicted to encode shorter polyprotein products lacking membrane and envelope structural proteins, and most of non-structural protein 1. Treatment with different broad-range antiviral nucleosides revealed that USUV is sensitive to these compounds in the context of a persistent infection, in agreement with previous observations during lytic infections. The exposure of infected cells to prolonged treatment (10 days) with favipiravir and/or ribavirin resulted in the complete clearance of infectivity in the cellular supernatants (decrease of ~5 log

Topics: Amides; Animals; Antiviral Agents; Chlorocebus aethiops; Flavivirus; Flavivirus Infections; Models, Biological; Pyrazines; Ribavirin; RNA, Viral; Sequence Analysis, DNA; Sequence Deletion; Serial Passage; Treatment Outcome; Vero Cells; Viral Load; Viral Proteins; Virus Cultivation; Virus Replication

Topics: Amides; Animal Structures; Animals; Antiviral Agents; Disease Models, Animal; Flavivirus; Flavivirus Infections; Mice; Microbial Sensitivity Tests; Pyrazines; Treatment Outcome; Viral Load; Virus Replication