Prophylactic protection from lethal henipavirus disease mediated by Nipah-derived defective interfering particles is influenced by challenge virus strain and viral species.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-01 Epub Date: 2025-08-25 DOI:10.1016/j.ebiom.2025.105897

Stephen R Welch, Jessica R Spengler, Jessica R Harmon, JoAnn D Coleman-McCray, Sarah C Genzer, Katherine A Davies, Teresa E Sorvillo, Florine E M Scholte, Sergio E Rodriguez, Joel M Montgomery, Stuart T Nichol, Christina F Spiropoulou

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引用次数: 0

Abstract

Background: Henipaviruses, including Nipah and Hendra viruses, are zoonotic pathogens that can cause severe respiratory and neurological diseases with high mortality rates in humans. Due to the severity of the disease, the high pandemic potential of these viruses, and the lack of approved treatments, the development of safe and effective medical countermeasures against henipaviruses is a critical priority.

Methods: Here, we evaluate treatment efficacy of defective interfering particles (DIPs)-naturally occurring virus-like particles that lack substantial portions of the viral genome-against henipaviruses in the Syrian hamster model of disease.

Findings: Prophylactic DIP treatment markedly reduced clinical signs and lethality in Syrian hamsters. Single or repeated pre-exposure regimens, starting up to 3 days before challenge, provided protection, while post-exposure treatment was ineffective. DIPs derived from NiV strain Malaysia were most effective against NiV Malaysia but also provided strong protection against the closely related NiV Bangladesh with certain regimens. However, these DIPs offered minimal or no protection against lethality from the more distantly related Hendra virus.

Interpretation: Our data indicate efficacy of DIPs as a pre-exposure prophylactic for henipavirus infection and support a direct mechanism of viral inhibition.

Funding: This work was partially supported by the DARPAINTERfering and Co-Evolving Prevention and Therapy (INTERCEPT) program (DARPA-BAA-16-35), CDC Emerging Infectious Disease Research Core Funds, an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC) administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC (K.A.D., S.E.R.), and by NIAID1R01AI151006 (T.E.S).

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由尼帕衍生的缺陷干扰颗粒介导的致命性希尼帕病毒病的预防保护受到攻毒病毒株和病毒种的影响。

背景：包括尼帕病毒和亨德拉病毒在内的亨尼帕病毒是人畜共患病原体，可引起人类严重的呼吸道和神经系统疾病，死亡率高。由于该病的严重性、这些病毒大流行的可能性高以及缺乏经批准的治疗方法，开发安全有效的针对亨尼帕病毒的医疗对策是一个关键的优先事项。方法：在这里，我们在叙利亚仓鼠疾病模型中评估缺陷干扰颗粒(DIPs)-天然存在的病毒样颗粒，缺乏病毒基因组的大部分-对亨尼帕病毒的治疗效果。结果：预防性DIP治疗显著降低了叙利亚仓鼠的临床症状和死亡率。单次或多次暴露前治疗方案，在攻击前3天开始，提供保护，而暴露后治疗无效。来自马来西亚NiV毒株的dip对马来西亚NiV最有效，但也通过某些方案对密切相关的孟加拉国NiV提供了强有力的保护。然而，这些dip对更远亲的亨德拉病毒的致命性提供了很少或根本没有保护。解释：我们的数据表明DIPs作为暴露前预防亨尼帕病毒感染的有效性，并支持病毒抑制的直接机制。资助:这项工作得到了DARPA-BAA-16-35、CDC新发传染病研究核心基金、橡树岭科学与教育研究所管理的疾病控制与预防中心（CDC）研究参与计划（美国能源部和CDC之间的机构间协议）和NIAID1R01AI151006 （T.E.S）的部分支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.