Ancient Ancestry of KFDV and AHFV Revealed by Complete Genome Analyses of Viruses Isolated from Ticks and Mammalian Hosts

Kimberly A Dodd,Serena A Carroll,Brian H Bird,Stuart T Nichol,César G Albariño,Pierre E Rollin,Marina L Khristova,Bobbie R Erickson,James A Comer,Rebeca Rico-Hesse

doi:10.1371/journal.pntd.0001352

Abstract

BackgroundAlkhurma hemorrhagic fever virus (AHFV) and Kyasanur forest disease virus (KFDV) cause significant human disease and mortality in Saudi Arabia and India, respectively. Despite their distinct geographic ranges, AHFV and KFDV share a remarkably high sequence identity. Given its emergence decades after KFDV, AHFV has since been considered a variant of KFDV and thought to have arisen from an introduction of KFDV to Saudi Arabia from India. To gain a better understanding of the evolutionary history of AHFV and KFDV, we analyzed the full length genomes of 16 AHFV and 3 KFDV isolates.Methodology/Principal FindingsViral genomes were sequenced and compared to two AHFV sequences available in GenBank. Sequence analyses revealed higher genetic diversity within AHFVs isolated from ticks than human AHFV isolates. A Bayesian coalescent phylogenetic analysis demonstrated an ancient divergence of AHFV and KFDV of approximately 700 years ago.Conclusions/SignificanceThe high sequence diversity within tick populations and the presence of competent tick vectors in the surrounding regions, coupled with the recent identification of AHFV in Egypt, indicate possible viral range expansion or a larger geographic range than previously thought. The divergence of AHFV from KFDV nearly 700 years ago suggests other AHFV/KFDV-like viruses might exist in the regions between Saudi Arabia and India. Given the human morbidity and mortality associated with these viruses, these results emphasize the importance of more focused study of these significant public health threats.

Highlights

Alkhurma hemorrhagic fever virus (AHFV) is a variant of Kyasanur Forest disease virus (KFDV), and like Kyasanur forest disease virus (KFDV), is a member of the mammalian tick-borne encephalitis group [family Flaviviridae, genus Flavivirus]
The host range of KFDV is quite different from AHFV; KFDV was first identified as the cause of nonhuman primate die-offs (Presbytis entellus and Macaca radiata) as well as a concurrent outbreak of fatal human disease in the Kyasanur forest region of India in 1957
AHFV was first identified in the mid1990s and due to its strong genetic similarity to KFDV it has since been considered the result of a recent introduction of KFDV into Saudi Arabia

Summary

Introduction

Alkhurma hemorrhagic fever virus (AHFV) is a variant of Kyasanur Forest disease virus (KFDV), and like KFDV, is a member of the mammalian tick-borne encephalitis group [family Flaviviridae, genus Flavivirus]. Human AHFV infections have been associated with tick bites, and AHFV has been isolated from an Ornithodoros tick in Jeddah [8], and Ornithodoros savignyi and Hyalomma dromedarii ticks in Najran [9] Another common risk factor for AHFV infection appears to be close contact with domestic animals, sheep and camels [5], no disease has been reported in livestock or other animals. Alkhurma hemorrhagic fever virus (AHFV) and Kyasanur forest disease virus (KFDV) cause significant human disease and mortality in Saudi Arabia and India, respectively. Despite their distinct geographic ranges, AHFV and KFDV share a remarkably high sequence identity. To gain a better understanding of the evolutionary history of AHFV and KFDV, we analyzed the full length genomes of 16 AHFV and 3 KFDV isolates

Methods

Results

Discussion

Conclusion