Circulation of Lassa virus across the endemic Edo-Ondo axis, Nigeria, with cross-species transmission between multimammate mice

Abstract

We phylogenetically compared sequences of the zoonotic Lassa virus (LASV) obtained from Mastomys rodents in seven localities across the highly endemic Edo and Ondo States within Nigeria. Sequencing 1641 nt from the S segment of the virus genome, we resolved clades within lineage II that were either limited to Ebudin and Okhuesan in Edo state (2g-beta) or along Owo-Okeluse-Ifon in Ondo state (2g-gamma). We also found clades within Ekpoma, a relatively large cosmopolitan town in Edo state, that extended into other localities within Edo (2g-alpha) and Ondo (2g-delta). LASV variants from M. natalensis within Ebudin and Ekpoma in Edo State (dated approximately 1961) were more ancient compared to those from Ondo state (approximately 1977), suggesting a broadly east-west virus migration across south-western Nigeria; a pattern not always consistent with LASV sequences derived from humans in the same localities. Additionally, in Ebudin and Ekpoma, LASV sequences between M. natalensis and M. erythroleucus were interspersed on the phylogenetic tree, but those from M. erythroleucus were estimated to emerge more recently (approximately 2005). Overall, our results show that LASV amplification in certain localities (reaching a prevalence as high as 76% in Okeluse), anthropogenically-aided spread of rodent-borne variants amidst the larger towns (involving communal accommodation such as student hostels), and virus-exchange between syntopic M. natalensis and M. erythroleucus rodents (as the latter, a savanna species, encroaches southward into the degraded forest) pose perpetual zoonotic hazard across the Edo-Ondo Lassa fever belt, threatening to accelerate the dissemination of the virus into non endemic areas.

Keywords: Lassa virus; Mastomys; Nigeria; emergence and spreading; host-switching.

Figure 1.

The Edo-Ondo Lassa fever belt. Red dots within the enlarged map indicate localities sampled in this study. Above each locality are stated the LASV clades resolved within sub-lineage 2 g (i.e. 2gα, 2gβ, 2gγ & 2gδ). Inserted is Nigeria with the region comprising Edo and Ondo States shaded red. Roman numerals within Nigeria denote geographic distribution of LASV lineages that, leading up to this study, were detected within Nigeria in the rodents Mastomys natalensis (lineage II), Mastomys erythroleucus (III) and Hylomyscus pamfi (VI) respectively.

Figure 2.

Phylogenetic tree of LASV sequences obtained from Mastomys rodents in the Edo-Ondo area. The analysis is based on a concatenated “S” sequence which includes partial glycoprotein and nucleoprotein fragments from 111 rodents. Two human-derived sequences were used as outgroups to show the sub-lineage 2f. Labels 2gα-δ identify ingroup clades. Ingroup sequences derived from M. natalensis are in labelled black, while those from M. erythroleucus are in red.

Figure 3.

Fine-scale LASV clade distribution within the larger-sized localities. Serial numbers represent sampling points (1–26 for Ekpoma, 1–10 for Ifon and 1–13 for Owo). Red sampling points within each map indicate where LASV-positive Mastomys were captured, with corresponding virus clades beside the sampling point number (e.g. 1: α, β, γ). Above each locality map appear details concerning the distribution of LASV sequences among sampling points and clades (e.g. 1: δ (88, 97, 109, 240, 271)), the virus prevalence in Mastomys at each LASV-positive address, and the mean sequence similarity. Circular sampling points denote private residences, and triangles communal residences. Data from 2011 to 2012 [25,29] are included for Ekpoma.

Figure 4.

Estimated dates of emergence for LASV sequences obtained from Mastomys rodents. (A) M. natalensis and M. erythroleucus in Ebudin. (B) M. natalensis in various localities.

Figure 5.

Estimated dates of emergence for LASV sequences obtained from humans.