Abstract
BackgroundThe tick-borne flavivirus, Kyasanur Forest disease virus (KFDV) causes seasonal infections and periodic outbreaks in south-west India. The current vaccine offers poor protection with reported issues of coverage and immunogenicity. Since there are no approved prophylactic therapeutics for KFDV, type I IFN-α/β subtypes were assessed for antiviral potency against KFDV in cell culture.Methodology/Principal FindingsThe continued passage of KFDV-infected cells with re-administered IFN-α2a treatment did not eliminate KFDV and had little effect on infectious particle production whereas the IFN-sensitive, green fluorescent protein-expressing vesicular stomatitis virus (VSV-GFP) infection was controlled. Further evaluation of the other IFN-α/β subtypes versus KFDV infection indicated that single treatments of either IFN-αWA and IFN-αΚ appeared to be more effective than IFN-α2a at reducing KFDV titres. Concentration-dependent analysis of these IFN-α/β subtypes revealed that regardless of subtype, low concentrations of IFN were able to limit cytopathic effects (CPE), while significantly higher concentrations were needed for inhibition of virion release. Furthermore, expression of the KFDV NS5 in cell culture before IFN addition enabled VSV-GFP to overcome the effects of IFN-α/β signalling, producing a robust infection.Conclusions/SignificanceTreatment of cell culture with IFN does not appear to be suitable for KFDV eradication and the assay used for such studies should be carefully considered. Further, it appears that the NS5 protein is sufficient to permit KFDV to bypass the antiviral properties of IFN. We suggest that other prophylactic therapeutics should be evaluated in place of IFN for treatment of individuals with KFDV disease.
Highlights
Kyasanur Forest disease virus (KFDV) is a tick-borne flavivirus that was identified in 1957 following a monkey epizootic and a coinciding human outbreak in south-west India [1]
Further characterization of the other IFNα/β subtypes used at different concentrations revealed that KFDV replication was insensitive to all subtypes, even though signs of cellular damage were reduced
KFDV cases previously were localized within the Shimoga district of Karnataka; KFDV has been recently discovered in the neighboring states of Kerala, Tamil Nadu, Goa and Maharashtra [2,3,4,5] and, possibly China in 1989 [6] increasing the potential public health risk associated with this pathogen
Summary
Kyasanur Forest disease virus (KFDV) is a tick-borne flavivirus that was identified in 1957 following a monkey epizootic and a coinciding human outbreak in south-west India [1]. A vaccine for KFDV is available for those living in affected areas and those living within a 5 kilometer radius of a positive case from either humans, monkeys or tick pools [7], but there has been issues with implementation and efficacy. With the annual number of cases ranging from 400– 500 and an associated fatality rate of 3–5% [10], there is a need for alternative therapeutic options, besides the current vaccine and tick bite prevention measures. The tick-borne flavivirus, Kyasanur Forest disease virus (KFDV) causes seasonal infections and periodic outbreaks in south-west India. Since there are no approved prophylactic therapeutics for KFDV, type I IFN-α/β subtypes were assessed for antiviral potency against KFDV in cell culture
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
