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抗逆转录病毒药物体外抗马传染性贫血病毒的疗效评估

Efficacy assessment of antiretroviral drugs against equine infectious anemia virus in vitro.

作者信息

Schimmich Cécile, Vabret Astrid, Valle-Casuso José-Carlos

机构信息

ANSES Animal Health Laboratory, PhEED Unit, Goustranville, France.

University of Caen Normandy, Dynamicure INSERM UMR 1311, Centre hospital-universitaire (CHU) Caen, Department of Virology, Caen, France.

出版信息

Virus Res. 2024 Dec;350:199503. doi: 10.1016/j.virusres.2024.199503. Epub 2024 Dec 11.

Abstract

Equine infectious anemia virus (EIAV) is an equine lentivirus related to human immunodeficiency virus type 1 (HIV-1). Both viruses are related among the Retroviridae family, but their clinical manifestations are different as EIAV causes a long persistent infection with no progressive immune dysfunction in most cases. Today, no treatment is approved against EIAV, contrary to HIV-1, manageable through antiretroviral therapy, known as HAART (highly active antiretroviral therapy) or cART (combination antiretroviral therapy). No information about the efficacy of antiretroviral drugs against EIAV is available in the literature. This study evaluates the in vitro antiviral effect of eighteen FDA-approved antiretroviral compounds from different drug families, in an equine cells in vitro infection model with EIAV reference strain. Equine dermal cells, as well as equine peripheral blood mononuclear cells were treated with non-cytotoxic drug concentrations and infected with EIAV. Relative virus release in culture supernatants was assessed through relative quantification of viral RNA via RTqPCR and viral DNA comprising proviral integration in the cell genome was assessed through qPCR of infected cells, both after nucleic acid extractions. Out of eighteen tested drugs, thirteen showed a significant antiviral effect against EIAV in vitro, an interesting discovery showing the similarities between HIV-1 and EIAV and opening a possibility to treat equine infectious anemia to avoid the disease spread.

摘要

马传染性贫血病毒(EIAV)是一种与1型人类免疫缺陷病毒(HIV-1)相关的马慢病毒。这两种病毒都属于逆转录病毒科,但它们的临床表现不同,因为EIAV在大多数情况下会引起长期持续感染,且不会出现进行性免疫功能障碍。如今,与HIV-1不同,尚无针对EIAV的获批治疗方法,HIV-1可通过抗逆转录病毒疗法(称为高效抗逆转录病毒疗法或cART,即联合抗逆转录病毒疗法)进行控制。文献中没有关于抗逆转录病毒药物对EIAV疗效的信息。本研究在一个用EIAV参考毒株进行体外感染的马细胞模型中,评估了来自不同药物家族的18种FDA批准的抗逆转录病毒化合物的体外抗病毒作用。用无细胞毒性的药物浓度处理马皮肤细胞以及马外周血单核细胞,然后用EIAV感染。在核酸提取后,通过RTqPCR对病毒RNA进行相对定量来评估培养上清液中的相对病毒释放,并通过对感染细胞进行qPCR来评估细胞基因组中包含前病毒整合的病毒DNA。在18种受试药物中,有13种在体外对EIAV显示出显著的抗病毒作用,这一有趣的发现显示了HIV-1和EIAV之间的相似性,并为治疗马传染性贫血以避免疾病传播开辟了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ce6/11699113/69c8e7b19074/gr1.jpg

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