Ecology of Lassa virus and related arenaviruses in the natural host Mastomys natalensis

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Lassa fever is a zoonotic disease caused by Lassa virus, an African arenavirus. The disease is endemic in West Africa and it is estimated that 100,000 infections occur each year as a result of transmission of Lassa virus from its rodent reservoir (Mastomys natalensis) to humans. Control measures aiming at reducing the virus prevalence in the rodent population could reduce the risk of rodent-to-human transmission. However, the course of infection, the dynamics of virus-rodent interaction, and modes of virus transmission among the rodent population are poorly understood. Therefore, a major objective of this research project is to enhance knowledge on rodent ecology to develop, in future, rodent-based intervention strategies that are applicable in the endemic area. Major objectives that were planned for the first stage and have been partially reached were: (1) description of basic infection parameters of Lassa virus and the related Morogoro and Mopeia viruses in vitro and in vivo (2) identification of virus host determinants important for persistence in the natural host (3) determination of modes and timing of transmission of the African arenaviruses among M. natalensis in the laboratory and in the field (Tanzania), using Morogoro virus as a feasible model, and (4) translation of this information into a mathematical model for Lassa virus transmission. The second phase is based on the results obtained so far. It is focused on (1) innate and adaptive immune mechanisms underlying the species barrier in immune cells of M. natalensis and the tolerance of neonatal animals towards infection with Morogoro and Mopeia viruses (2) relevance of the viral interferon antagonist for productive replication and persistence of Lassa, Morogoro, and Mopeia viruses in vitro and in vivo (3) longitudinal studies of arenavirus transmission in the wild, using both existing and new data (4) adjusting the preliminary models by including individual variation in shedding and contact rates, spatial variation and environmental stochasticity and (5) searching for ecological factors to explain the persistence of closely related arenaviruses in sympatric and closely related, but different, rodent species. The resulting model shall be used to predict the abundance threshold and environmental conditions below which the virus cannot persist in the natural host population.