Lassa virus immunology in the natural host, Mastomys natalensis
Lassa virus (LASV) outbreaks are primarily driven by zoonotic transmission from infected rodents to humans. It is therefore crucial to understand the virus dynamics and transmission patterns in the natural rodent reservoir to establish effective preventive measures and accurately predict LASV outbreaks. However, no adequate data exist on the mode of transmission (vertical, perinatal, in adulthood, sexual) of LASV among the natural host population (Mastomys natalensis), the period of infectivity (persistent for life or limited) and the relation between rodent density and the prevalence of the virus in the rodent population. These parameters have dramatic effects on the outcome of ecological disease models. Knowing how a virus is transmitted is crucial to develop useful models that can predict how, how fast and when the infection will spread in a host population.
We investigate the viral dynamics in M. natalensis following the infection with LASV and related arenaviruses, analyzing virus loads in body fluids and organs over time. Furthermore, we aim to assess transmission patterns between infected individuals and exposed contacts (Figure 1). The second objective of this project is the characterization of the host immune response following arenavirus infection. We use a variety of tools to identify host factors that are important for virus clearance or the development of persistent infections.
Characterization of host-species barriers in Arenavirus infection
Apart from Mastomys natalensis, Lassa virus has also been found in several other rodent species, like M. erythroleucus, Hylomyscus pamfi, or Mus baoulei. The widespread presence of its main reservoir and the existence of additional reservoir hosts contributes to the epidemic potential of LASV. Determining virus and host factors important for potential virus-host barriers and spillover infections into new reservoir hosts is essential to develop & implement accurate surveillance systems for LASV outbreaks.
In a second project we compare homologous (derived from M. natalensis) and heterologous (derived from other rodent species) arenavirus infections in vivo and in vitro, in order to observe which adaptative mutations might occur during adaptation processes. Furthermore, chimeric LASV will be created to assess the contribution of each arenaviral protein in an infectious context. Besides examining full virus particles, we investigate, which steps of the viral life cycle, such as entry, replication and transcription, as well as assembly of virions and budding are of importance for virus-host-adaptation to new hosts.