Abstract
Genome reassortment in Lassa virus (LASV) has been reported in nature, but phenotypic consequences of this phenomenon are not well described. Here we characterize, both in vitro and in vivo, reassortment between 2 LASV strains: the prototypic 1976 Josiah strain and a more recently isolated 2015 Liberian strain. In vitro analysis showed that although cis- and trans-acting elements of viral RNA synthesis were compatible between strains, reassortants demonstrated different levels of viral replication. These differences were also apparent in vivo, as reassortants varied in pathogenicity in the guinea pig model of LASV infection. The reassortant variant containing the Josiah S segment retained the virulence of the parental Josiah strain, but the reassortant variant containing the S segment of the Liberian isolate was highly attenuated compared to both parental strains. Contrary to observations in reassortants between LASV and other arenavirus species, which suggest that L segment-encoded factors are responsible for virulence, these studies highlight a role for S segment-encoded virulence factors in disease, and also suggest that inefficient interactions between proteins of heterologous strains may limit the prevalence of reassortant LASV variants in nature.
Highlights
Lassa virus (LASV, family Arenaviridae, genus Mammarenavirus) is the etiological agent of Lassa fever (LF), an acute zoonotic viral hemorrhagic fever endemic in West Africa
Investigations into LASV reassortment have been limited to interspecies studies using LASV and another closely related old world arenavirus, Mopeia virus (MOPV) (Lukashevich, 1992; Lukashevich et al, 2005) While these studies provided key support for the potential of arenavirus reassortment and introduced a novel vaccine candidate, none have focused on LASV interspecies reassortment
To conduct initial investigations into intraspecies reassortment of LASV, our studies focused on intraclade reassortment between the Josiah strain, an isolate from a 1976 case of LF in Segbwema, Sierra Leone (Wulff and Johnson, 1979; Albariño et al, 2011) and a geographically and phenotypically related NJ2015 isolate, obtained from a LF case imported into USA in 2015
Summary
Lassa virus (LASV, family Arenaviridae, genus Mammarenavirus) is the etiological agent of Lassa fever (LF), an acute zoonotic viral hemorrhagic fever endemic in West Africa. The first documented case occurred in 1969 in the area around Jos, Nigeria (Frame et al, 1970). The disease was soon recognized as being endemic in several West African countries, including Nigeria (Omilabu et al, 2005), Sierra Leone (Shaffer et al, 2014), Guinea (Kernéis et al, 2009), and Liberia (Frame et al, 1984; Monson et al, 1984). Of the 100,000–300,000 estimated annual cases of LF, approximately 5,000 result in death (McCormick et al, 1987).
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