Abstract

The Kyasanur Forest Disease (KFD) has become a major public health problem in the State of Karnataka, India where the disease was first identified and in Tamil Nadu, Maharashtra, Kerala, and Goa covering the Western Ghats region of India. The incidence of positive cases and distribution of the Kyasanur Forest Disease virus (KFDV) in different geographical regions raises the need to understand the evolution and spatiotemporal transmission dynamics. Phylogeography analysis based on 48 whole genomes (46 from this study) and additionally 28 E-gene sequences of KFDV isolated from different regions spanning the period 1957–2017 was thus undertaken. The mean evolutionary rates based the E-gene was marginally higher than that based on the whole genomes. A subgroup of KFDV strains (2006–2017) differing from the early Karnataka strains (1957–1972) by ~2.76% in their whole genomes and representing spread to different geographical areas diverged around 1980. Dispersal from Karnataka to Goa and Maharashtra was indicated. Maharashtra represented a new source for transmission of KFDV since ~2013. Significant evidence of adaptive evolution at site 123 A/T located in the vicinity of the envelope protein dimer interface may have functional implications. The findings indicate the need to curtail the spread of KFDV by surveillance measures and improved vaccination strategies.

Highlights

  • The Kyasanur Forest Disease virus (KFDV) has a positive-sense, single-stranded RNA genome which is approximately 11 kb in length and encodes a single 3416 aa polyprotein that is cleaved post-translationally into a total of three structural and seven non-structural (NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5) proteins[8]

  • It was found that almost 4–65% of reads were of KFDV origin depending on the viral load and the quality of the RNA library (Supplementary Table S2)

  • It was further noted that more KFDV reads were retrieved in the Tissue culture Fluid (TCF) as compared to KFDV reads from mice brain suspension which may be due to contamination with the host sequences

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Summary

Introduction

The KFDV has a positive-sense, single-stranded RNA genome which is approximately 11 kb in length and encodes a single 3416 aa polyprotein that is cleaved post-translationally into a total of three structural (capsid C, pre-membrane prM, which is the glycosylated precursor to a small transmembrane protein M and envelope E) and seven non-structural (NS1, NS2a, NS2b, NS3, NS4a, NS4b and NS5) proteins[8]. Recent studies demonstrate the existence of KFDV in the States neighboring Karnataka including Kerala, Tamil Nadu, Goa, and Maharashtra[4], which indicates the prevalence or spread of the KFDV arena to the nearby geographical locations. The isolates were collected from different geographic locations, covering the first KFDV isolation in Karnataka and the affected neighboring districts, and from the other affected States of Goa, Tamil Nadu, and Maharashtra. Additional E-gene sequences of viruses available from the State of Kerala were included in a phylogeography study of an enlarged E-gene dataset Such phylogeography studies for KFDV based on time-sampled isolates from the States of Karnataka, Maharashtra, Goa, Tamil Nadu and Kerala are important to understand the dispersal pattern of the virus within Karnataka and its spread to the other locations

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