Genome and phylogeny

The genome of LASV is composed by 2 ambisense segments: the smaller segment (S) codes for the glycoprotein precursor and the nucleoprotein, and the larger segment (L) codes for the polymerase and the matrix protein. The coding regions are separated by an intergenic region with a strong secondary structure, and are flanked by non-coding regions. In 2000, Bowen et al. proposed a classification of the different strains with a phylogeny based on the GP, NP and polymerase. They suggested the existence of four lineages; 3 in Nigeria and 1 in the Sierra Leone-Liberia-Guinea.

Discovery of new hosts

In 2014, we discovered two new hosts: Mastomys erythroleucus in Guinea and in Nigeria, and Hylomyscus pamfi in Nigeria. In 2013 and 2019, we described the pygmy mouse, Mus (Nannomys) baoulei, as a possible carrier of a new LASV lineage in Ghana and in Benin (Figure 6).

Figure 6: Tree showing the different LASV strains derived from the rodent hosts (adapted from Olayemi and Fichet-Calvet, 2020). Photos: M. natalensis and H. pamfi (E. Fichet-Calvet), M. erythroleucus (JM Duplantier), Mus baoulei (F. Veyrunes).
Figure 6: Tree showing the different LASV strains derived from the rodent hosts (adapted from Olayemi and Fichet-Calvet, 2020). Photos: M. natalensis and H. pamfi (E. Fichet-Calvet), M. erythroleucus (JM Duplantier), Mus baoulei (F. Veyrunes).
©Fichet-Calvet

Discovery of new lineages

Investigations developed at ISTH in Nigeria revealed that some individuals had been infected with the Kako strain discovered in H. pamfi. The Kako strain therefore constitutes a new lineage because it is very distant from the lineage I discovered in 1969. Moreover, the recent Lassa epidemics in Benin and Togo (2014-2018) have shown that the patients were infected by a new strain, which forms a distinct 7th lineage (Figure 7).

 

Figure 7: Phylogeny of Lassa virus showing the new lineages VI and VII in Nigeria and Benin. Lineage VIII is putative until human cases infected with this strain are discovered. The tree is using the nucleoprotein (in Yadoudelon et al. 2020).
Figure 7: Phylogeny of Lassa virus showing the new lineages VI and VII in Nigeria and Benin. Lineage VIII is putative until human cases infected with this strain are discovered. The tree is using the nucleoprotein (in Yadoudelon et al. 2020).
©Fichet-Calvet

LASV evolution at a local scale

In Upper Guinea, a longitudinal survey has been performed during 10 years. Viruses circulating in a specific locality are diverse and polyphyletic with respect to viruses from neighbouring villages. However, there are monophyletic clusters formed by viruses from a village at specific points in time, indicating that the temporal and spatial pattern of LASV evolution in the natural reservoir is characterized by a combination of stationary circulation within a village and virus movement between villages.
 

LASV emergence per host: human versus rodent

Here, we seek to phylogenetically infer ancestry and descent between LASV sequences detected in rodents and humans in selected localities within West Africa in order to provide increased insight into virus transmission at the rodent-human boundary.

Figure 8: Dates of LASV emergence in Mastomys natalensis versus Homo sapiens living in (a) Ekpoma (Nigeria), and (b) Kenema (Sierra Leone). In both locations, the peak in humans shows the emergence of LASV earlier than the one in rodents (in Olayemi et al
Figure 8: Dates of LASV emergence in Mastomys natalensis versus Homo sapiens living in (a) Ekpoma (Nigeria), and (b) Kenema (Sierra Leone). In both locations, the peak in humans shows the emergence of LASV earlier than the one in rodents (in Olayemi et al. 2020).
©Fichet-Calvet

Our aim is to compile a dataset including LASV sequences collected from both humans and Mastomys rodents within distinctive hotspots of Lassa fever.
In a first study we phylogenetically compared LASV sequences obtained in two localities: Ekpoma in Nigeria and Kenema in Sierra Leone. We performed a time-calibrated phylogeny, using a Bayesian analysis on 198 taxa including 102 sequences from rodents and 96 from humans. Contrary to expectation, our results show that LASV strains detected in humans within these localities, even those sampled recently, are consistently ancient to those circulating in rodents in the same area (Figure 8).
Therefore, our results may suggest the occurrence of human-to-rodent transmission (reverse zoonosis).  

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