Molecular characterization of human pathogenic bunyaviruses of the Nyando and Bwamba/Pongola virus groups leads to the genetic identification of Mojuí dos Campos and Kaeng Khoi virus.

Allison Groseth,Eric Dahlstrom,Carla Weisend,Stephen F Porcella,Hideki Ebihara,Brandy J Russell,Robert B Tesh,Veena Mampilli,Remi Charrel

doi:10.1371/journal.pntd.0003147

Abstract

BackgroundHuman infection with Bwamba virus (BWAV) and the closely related Pongola virus (PGAV), as well as Nyando virus (NDV), are important causes of febrile illness in Africa. However, despite seroprevalence studies that indicate high rates of infection in many countries, these viruses remain relatively unknown and unstudied. In addition, a number of unclassified bunyaviruses have been isolated over the years often with uncertain relationships to human disease.Methodology/Principal FindingsIn order to better understand the genetic and evolutionary relationships among orthobunyaviruses associated with human disease, we have sequenced the complete genomes for all 3 segments of multiple strains of BWAV (n = 2), PGAV (n = 2) and NDV (n = 4), as well as the previously unclassified Mojuí dos Campos (MDCV) and Kaeng Khoi viruses (KKV). Based on phylogenetic analysis, we show that these viruses populate 2 distinct branches, one made up of BWAV and PGAV and the other composed of NDV, MDCV and KKV. Interestingly, the NDV strains analyzed form two distinct clades which differed by >10% on the amino acid level across all protein products. In addition, the assignment of two bat-associated bunyaviruses into the NDV group, which is clearly associated with mosquito-borne infection, led us to analyze the ability of these different viruses to grow in bat (RE05 and Tb 1 Lu) and mosquito (C6/36) cell lines, and indeed all the viruses tested were capable of efficient growth in these cell types.Conclusions/SignificanceOn the basis of our analyses, it is proposed to reclassify the NDV strains ERET147 and YM176-66 as a new virus species. Further, our analysis definitively identifies the previously unclassified bunyaviruses MDCV and KKV as distinct species within the NDV group and suggests that these viruses may have a broader host range than is currently appreciated.

Highlights

The Bunyaviridae are a large, diverse group of more than 350 viruses divided into 5 genera, of which more than 150 belong to the genus Orthobunyavirus [1]
In order to better understand orthobunyavirus evolution as it relates to the relationships between and degree of diversity among Bwamba virus (BWAV), Pongola virus (PGAV) and Nyando virus (NDV), we have determined the complete genome sequences for all 3 viral RNA segments from multiple strains of each of these viruses
Based on phylogenetic analysis of these viruses in relation to previously published data obtained from GenBank for other members of the genus Orthobunyavirus (Table S1), it is apparent that BWAV and PGAV form a distinct virus clade, separate from that formed by the NDV strains (Figure 2), consistent with their assignment to distinct serogroups

Summary

Introduction

The Bunyaviridae are a large, diverse group of more than 350 viruses divided into 5 genera, of which more than 150 belong to the genus Orthobunyavirus [1] These viruses represent a significant cause of arthropod-borne human disease worldwide, with infection often associated with a febrile and/or encephalitic illness, and in rare cases hemorrhagic manifestations [2]. Despite their importance for public health, from both a genetic and an evolutionary standpoint the family has been only poorly characterized. A number of unclassified bunyaviruses have been isolated over the years often with uncertain relationships to human disease

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Results

Conclusion