Maruyama Junki, Reyna Rachel A, Kishimoto-Urata Megumi, Urata Shinji, Manning John T, Harsell Nantian, Cook Rebecca, Huang Cheng, Nikolich-Zugich Janko, Makishima Tomoko, Paessler Slobodan
Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
Department of Otolaryngology, The University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS Pathog. 2022 May 23;18(5):e1010557. doi: 10.1371/journal.ppat.1010557. eCollection 2022 May.
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.
拉沙病毒（LASV）是拉沙热（LF）的病原体，严重时会引发致命的出血性疾病。幸存者中由LASV导致的听力损失是巨大的社会经济负担，然而，导致听力损失的机制尚不清楚。在本研究中，我们在小鼠拉沙热模型中使用听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）评估听觉功能，以确定LASV导致听力损失的潜在机制。在此过程中，我们率先在生物安全4级（BSL-4）设施中对啮齿动物进行ABR和DPOAE测试。我们的T细胞耗竭研究表明，CD4 T细胞在LASV导致的听力损失中起重要作用，而CD8 T细胞在LASV感染急性期的致病性方面至关重要。本研究结果可能有助于制定未来针对急性疾病和LASV导致的听力损失的应对措施。
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