Nigeria experiences annual outbreaks of Lassa fever (LF) with high case numbers. At least three clades of Lassa virus (LASV) have been documented in Nigeria, though recent outbreaks are most often associated with clade II or clade III viruses. Using a recently isolated clade III LASV from a case of LF in Nigeria in 2018, we developed and characterized a guinea pig adapted virus capable of causing lethal disease in commercially available Hartley guinea pigs. Uniform lethality was observed after four passages of the virus and was associated with only two dominant genomic changes. The adapted virus was highly virulent with a median lethal dose of 10 median tissue culture infectious doses. Disease was characterized by several hallmarks of LF in similar models including high fever, thrombocytopenia, coagulation disorders, and increased inflammatory immune mediators. High viral loads were noted in all solid organ specimens analyzed. Histological abnormalities were most striking in the lungs and livers of terminal animals and included interstitial inflammation, edema, and steatosis. Overall, this model represents a convenient small animal model for a clade III Nigeria LASV with which evaluation of specific prophylactic vaccines and medical countermeasures can be conducted.

Empirical data from survivors of Lassa fever and experimental disease modeling efforts, particularly those using mouse models, are at odds with respect to T cell–mediated pathogenesis. In mice, T cells have been shown to be imperative in disease progression and lethality, whereas in humans, an early and robust T cell response has been associated with survival. Here, we assessed the role of CD4 ⁺ and CD8 ⁺ T cells on disease progression and severity of Lassa virus infection in a nonhuman primate model. Using an antibody-mediated T cell depletion strategy prior to and after inoculation, we were able to examine Lassa virus infection in the absence of specific T cell responses. In animals depleted for either CD4 ⁺ or CD8 ⁺ T cells, Lassa virus infection remained uniformly lethal, with only a slight delay in disease progression was observed in the CD4-depleted group when compared with nondepleted controls. Milder pulmonary pathology was noticed in the absence of CD4 ⁺ or CD8 ⁺ T cells. Overall, our findings suggest that T cells have a limited effect on the development of Lassa fever in nonhuman primates.