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Lassa virus (LASV) is the causative agent of Lassa fever (LF), which presents as a lethal hemorrhagic disease in severe cases. LASV-induced hearing loss in survivors is a huge socioeconomic burden, however, the mechanism(s) leading to hearing loss is unknown. In this study, we evaluate in a mouse LF model the auditory function using auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to determine the mechanisms underlying LASV-induced hearing loss. In the process, we pioneered measures of ABR and DPOAE tests in rodents in biosafety level 4 (BSL-4) facilities. Our T cell depletion studies demonstrated that CD4 T-cells play an important role in LASV-induced hearing loss, while CD8 T-cells are critical for the pathogenicity in the acute phase of LASV infection. Results presented in this study may help to develop future countermeasures against acute disease and LASV-induced hearing loss. Author summary: Lassa virus (LASV) is known to cause lethal hemorrhagic fever, Lassa fever, and is classified into Risk Group-4 agents, which need to be handled in biosafety level-4 (BSL-4) due to its high pathogenicity. LASV is also known to cause hearing loss in patients. Hearing loss caused by LASV infection has a huge impact on patients' quality of life and socioeconomics in endemic areas, however, its mechanism is unknown. In order to unveil the mechanisms underlying hearing loss in Lassa fever patients, we used auditory tests, which are also used in newborn screening, in a mouse model of Lassa fever and revealed that LASV causes hearing loss with the combination of virus replication and host immune response and that CD4 T-cells have an important role in LASV-induced hearing loss. This new finding gives us a new insight to develop vaccines against Lassa fever and also therapeutic methods to prevent hearing loss induced by LASV infection in the future. [ABSTRACT FROM AUTHOR]