Background
Pathogenic hantaviruses geographically distributed in the Old World cause hemorrhagic fever with renal syndrome (HFRS), whereas New World hantaviruses are the etiological agents of hantavirus cardiopulmonary syndrome (HCPS). Ribavirin, a drug associated with toxicities, is presently indicated for treatment of HFRS, while treatment of the more frequently lethal HCPS is limited to supportive care. Because of the need for safe and effective antivirals to treat severe hantaviral infections, we evaluated favipiravir (T-705) against Dobrava and Maporal viruses as representative Old World and New World hantaviruses, respectively. Dobrava virus causes HFRS in Europe. Maporal virus (MPRLV), recently isolated from western Venezuela, is very similar phylogenetically to Andes virus (ANDV), the principal cause of HCPS in Argentina. Presently, there is no evidence that MPRLV can cause disease in humans.
Methods and Results
Here, we show that infection of Vero E6 cells with MPRLV is dependent on β3 integrins, similar to that reported for pathogenic hantaviruses. Further, by analysis of genetic determinants associated with the G1 glycoprotein cytoplasmic tail, we show the close genetic proximity of MPRLV to other HCPS-causing hantaviruses in these regions predictive of pathogenicity. Using focus-forming unit assays and measuring viral RNA by quantitative RT-PCR, we demonstrate anti-hantavirus activity by favipiravir with inhibitory concentrations ranging from 65 - 93 μM and selectivity indices > 50.
Conclusions
Our data suggest that MPRLV may serve as a safer alternative to modeling infection caused by the highly lethal ANDV and that hantaviruses are sensitive to the effects of favipiravir in cell culture.