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[人巨细胞病毒感染管理中的挑战与进展]

[Challenges and advances in the management of HCMV infections].

作者信息

Gourin Claire, Flores Thelma, Mafi Sarah, Malnou Cécile, Alain Sophie, Hantz Sébastien, Ligat Gaetan

机构信息

Inserm, CHU Limoges, Université de Limoges, Resinfit, U1092, Limoges, France.

Institut toulousain des Maladies infectieuses et inflammatoires (Infinity), Université de Toulouse, Inserm, CNRS, UPS, Toulouse, France.

出版信息

Virologie (Montrouge). 2024 Oct 1;28(5):309-325. doi: 10.1684/vir.2024.1063.

Abstract

Human cytomegalovirus (HCMV) is one of the most important causes of complications in immunocompromised patients and congenital infections. HCMV could also represent an interesting target for treatment to limit the progression of glioblastoma, a highly aggressive tumor. Ganciclovir, foscarnet and cidofovir, which interfere with the activity of the viral polymerase pUL54, are widely used in the treatment of transplant patients. However, their use in pregnant women remains limited or even contraindicated. On the other hand, hyperimmune immunoglobulins and valaciclovir have been shown to have a protective effect on the fetus. However, the toxicity of these treatments and the emergence of resistance mean that new therapeutic strategies need to be identified. Letermovir and maribavir have been developed to inhibit new targets, respectively the terminase complex and UL97 protein kinase. Their respective indications are the prevention of HCMV infection in haematopoietic stem cell transplant patients and the treatment of refractory HCMV infections. Finally, with the development of mRNA vaccines, the hope of one day seeing a prophylactic HCMV vaccine has never been greater. New therapeutic approaches are also being explored, but they still require extensive preclinical and clinical evaluation.

摘要

人巨细胞病毒(HCMV)是免疫功能低下患者并发症和先天性感染的最重要原因之一。HCMV也可能是限制胶质母细胞瘤(一种高度侵袭性肿瘤)进展的治疗的一个有吸引力的靶点。干扰病毒聚合酶pUL54活性的更昔洛韦、膦甲酸钠和西多福韦广泛用于移植患者的治疗。然而,它们在孕妇中的使用仍然有限甚至被禁止。另一方面,高免疫球蛋白和伐昔洛韦已被证明对胎儿有保护作用。然而,这些治疗的毒性和耐药性的出现意味着需要确定新的治疗策略。来特莫韦和马里巴韦已被开发用于抑制新的靶点,分别是端粒酶复合物和UL97蛋白激酶。它们各自的适应症是预防造血干细胞移植患者的HCMV感染和治疗难治性HCMV感染。最后,随着mRNA疫苗的发展,有朝一日看到预防性HCMV疫苗的希望从未如此之大。新的治疗方法也在探索中,但仍需要广泛的临床前和临床评估。

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