Next-generation sequencing of southern African Crimean-Congo haemorrhagic fever virus isolates reveals a high frequency of M segment reassortment

Abstract

SUMMARYCrimean Congo haemorrhagic fever virus (CCHFV) is a bunyavirus with a single-stranded RNA genome consisting of three segments (S, M, L), coding for the nucleocapsid protein, envelope glycoproteins and RNA polymerase, respectively. To date only five complete genome sequences are available from southern African isolates. Complete genome sequences were generated for 10 southern African CCHFV isolates using next-generation sequencing techniques. The maximum-likelihood method was used to generate tree topologies for 15 southern African plus 26 geographically distinct complete sequences from GenBank. M segment reassortment was identified in 10/15 southern African isolates by incongruencies in grouping compared to the S and L segments. These reassortant M segments cluster with isolates from Asia/Middle East, while the S and L segments cluster with strains from South/West Africa. The CCHFV M segment shows a high level of genetic diversity, while the S and L segments appear to co-evolve. The reason for the high frequency of M segment reassortment is not known. It has previously been suggested that M segment reassortment results in a virus with high fitness but a clear role in increased pathogenicity has yet to be shown.

Phylogeography of Crimean Congo Hemorrhagic Fever Virus

“…There was apparently no limit on the compatibility of segments, because reassortment could involve distantly related viruses that branched close to the tree root. There have been reports on reassortment between the S and L segments [9], but also suggestions of S and L segment co-evolution [22, 23]. In our dataset, there was no evidence that reassortment between the S and L segments was less frequent than that between the L and M segments.…”

“…Segment reassortment in CCHFV was first described over a decade ago [5] and has been confirmed in subsequent studies [3, 6, 22]. An increase of sequence samples over time provided evidence of more and more common reassortment.…”

Ectoparasitic Viral Zoonoses in the Southern African Context

“…(Table 2) illustrates the full viral classification of CCHFV [14,25]. This specific virus has a negative sense, singlestranded RNA genome which is circular and ambisense with three segments, namely large (L), middle (M) and small (S).…”

“…This specific virus has a negative sense, singlestranded RNA genome which is circular and ambisense with three segments, namely large (L), middle (M) and small (S). A recent research study conducted in South Africa has revealed high frequency reassortment in the M segment and further studies are needed to relate this to a competitive advantage such as increased transmissibility and enhanced pathogenicity [14]. When population genetics are considered, CCHFV is one of the most genetically diverse of the arboviruses and reassortment is widely described within its Bunyaviridae family [26].…”

“…The first indigenous case of CCHF was reported in 1981 but remains uncommon amongst humans although there is widespread evidence of it in animals throughout much of South Africa [12,13]. A recent research study from South Africa has shown promising data of a high frequency of reassortment in a selected genetic cluster of this viral member of the Bunyaviridae family that may relate particularly to its pathogenicity and transmissibility [14].…”