Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, 21218, USA.
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Rm E5636, Baltimore, MD, 21205, USA.
Sci Rep. 2023 Apr 20;13(1):6463. doi: 10.1038/s41598-023-33572-7.
Measles is a systemic disease initiated in the respiratory tract with widespread measles virus (MeV) infection of lymphoid tissue. Mortality can be substantial, but no licensed antiviral therapy is available. We evaluated both post-exposure prophylaxis and treatment with remdesivir, a broad-spectrum antiviral, using a well-characterized rhesus macaque model of measles. Animals were treated with intravenous remdesivir for 12 days beginning either 3 days after intratracheal infection (post-exposure prophylaxis, PEP) or 11 days after infection at the onset of disease (late treatment, LT). As PEP, remdesivir lowered levels of viral RNA in peripheral blood mononuclear cells, but RNA rebounded at the end of the treatment period and infectious virus was continuously recoverable. MeV RNA was cleared more rapidly from lymphoid tissue, was variably detected in the respiratory tract, and not detected in urine. PEP did not improve clinical disease nor lymphopenia and reduced the antibody response to infection. In contrast, LT had little effect on levels of viral RNA or the antibody response but also did not decrease clinical disease. Therefore, remdesivir transiently suppressed expression of viral RNA and limited dissemination when provided as PEP, but virus was not cleared and resumed replication without improvement in the clinical disease parameters evaluated.
麻疹是一种全身性疾病，始于呼吸道，伴有广泛的麻疹病毒（MeV）感染淋巴组织。死亡率可能很高，但目前尚无获得许可的抗病毒疗法。我们使用经过充分表征的猕猴麻疹模型，评估了暴露后预防和使用瑞德西韦（一种广谱抗病毒药物）治疗的效果。动物在鼻内感染后 3 天（暴露后预防，PEP）或感染后 11 天（疾病开始时，即晚期治疗，LT）开始静脉内给予瑞德西韦治疗 12 天。作为 PEP，瑞德西韦降低了外周血单核细胞中的病毒 RNA 水平，但在治疗期末，RNA 反弹，并且持续可回收感染性病毒。MeV RNA 从淋巴组织中清除得更快，在呼吸道中呈可变检测，在尿液中未检测到。PEP 并未改善临床疾病或淋巴细胞减少症，也未降低对感染的抗体反应。相比之下，LT 对病毒 RNA 水平或抗体反应几乎没有影响，但也不会降低临床疾病。因此，瑞德西韦作为 PEP 使用时可短暂抑制病毒 RNA 的表达和传播，但病毒并未清除，且在未改善评估的临床疾病参数的情况下恢复复制。
