Emergence of a novel chikungunya virus strain bearing the E1:V80A substitution, out of the Mombasa, Kenya 2017-2018 outbreak

Abstract

Between late 2017 and mid-2018, a chikungunya fever outbreak occurred in Mombasa, Kenya that followed an earlier outbreak in mid-2016 in Mandera County on the border with Somalia. Using targeted Next Generation Sequencing, we obtained genomes from clinical samples collected during the 2017/2018 Mombasa outbreak. We compared data from the 2016 Mandera outbreak with the 2017/2018 Mombasa outbreak, and found that both had the Aedes aegypti adapting mutations, E1:K211E and E2:V264A. Further to the above two mutations, 11 of 15 CHIKV genomes from the Mombasa outbreak showed a novel triple mutation signature of E1:V80A, E1:T82I and E1:V84D. These novel mutations are estimated to have arisen in Mombasa by mid-2017 (2017.58, 95% HPD: 2017.23, 2017.84). The MRCA for the Mombasa outbreak genomes is estimated to have been present in early 2017 (2017.22, 95% HPD: 2016.68, 2017.63). Interestingly some of the earliest genomes from the Mombasa outbreak lacked the E1:V80A, E1:T82I and E1:V84D substitutions. Previous laboratory experiments have indicated that a substitution at position E1:80 in the CHIKV genome may lead to increased CHIKV transmissibility by Ae. albopictus. Genbank investigation of all available CHIKV genomes revealed that E1:V80A was not present; therefore, our data constitutes the first report of the E1:V80A mutation occurring in nature. To date, chikungunya outbreaks in the Northern and Western Hemispheres have occurred in Ae. aegypti inhabited tropical regions. Notwithstanding, it has been suggested that an Ae. albopictus adaptable ECSA or IOL strain could easily be introduced in these regions leading to a new wave of outbreaks. Our data on the recent Mombasa CHIKV outbreak has shown that a potential Ae. albopictus adapting mutation may be evolving within the East African region. It is even more worrisome that there exists potential for emergence of a CHIKV strain more adapted to efficient transmission by both Ae. albopictus and Ae.aegypti simultaneously. In view of the present data and history of chikungunya outbreaks, pandemic potential for such a strain is now a likely possibility in the future. Thus, continued surveillance of chikungunya backed by molecular epidemiologic capacity should be sustained to understand the evolving public health threat and inform prevention and control measures including the ongoing vaccine development efforts.

Fig 1. Maximum likelihood phylogenetic tree based on the complete-coding region of the four CHIKV lineages.

The Mombasa 2017 outbreak genomes are highlighted in red and the Mandera outbreak strain is highlighted in blue. The Lamu/Mombasa 2004 strains are shown in green. The ECSA lineage with tip-labels is expanded.

Fig 2. Maximum clade credibility (MCC) tree generated using BEAST analysis.

Generated using 130 CHIKV sequences of the ECSA lineage. Mombasa genomes with E1:V80A, E1:T82I and E1:V84D mutations are shown in red, while those lacking these mutations are shown in pink.

Fig 3

Protein figures showing; A) ribbon representation of CHIKV E1-E2 heterodimer (ID: 3N42) with the E1 monomer represented in blue and the E2 monomer represented in orange. Amino acid residues with potential functional significance are represented in spheres within the figure. B) Surface representation of the same E1-E2 heterodimer showing, i) wild type amino acids and ii) the reported mutations.