van de Sande Wendy W J, Vonk Alieke G
ErasmusMC, Department of Medical Microbiology and Infectious Diseases, Wytemaweg 80, 3015 CE Rotterdam, The Netherlands.
Med Mycol. 2019 Apr 1;57(Supplement_2):S179-S188. doi: 10.1093/mmy/myy073.
With the current revived interest in the use of bacteriophages for the treatment of bacterial infections, the study of mycoviruses as novel therapeutic solutions for invasive aspergillosis is the logical next step. Although ssRNA, dsRNA, and ssDNA mycoviruses have been identified, the majority of characterised mycoviruses have dsRNA genomes. Prevalence of dsRNA mycoviruses in Aspergillus spp. varies, and mycoviruses can have different effects on their fungal hosts: hypovirulence, hypervirulence, or a killer phenotype. Therapeutically, extracellular transmission of the mycovirus is essential. DsRNA mycoviruses lack an extracellular phase; however, a single ssDNA mycovirus with homologues in Aspergillus genomes has been described with an extracellular mode of transmission. Mycoviruses can induce hypovirulence or a killer phenotype, and both can be exploited therapeutically. Mycoviruses inducing hypovirulence have been used to control chestnut blight, however for aspergillosis no such mycovirus has been identified yet. Mycovirus encoded killer toxins or anti-idiotypic antibodies and killer peptides derived from these have been demonstrated to control fungal infections including aspergillosis in animals. This indicates that mycoviruses inducing both phenotypes could be exploited therapeutically as long as the right mycovirus has been identified.
随着当前对使用噬菌体治疗细菌感染的兴趣再度兴起,将真菌病毒作为侵袭性曲霉病的新型治疗方案进行研究是顺理成章的下一步。尽管已鉴定出单链RNA、双链RNA和单链DNA真菌病毒,但大多数已表征的真菌病毒具有双链RNA基因组。双链RNA真菌病毒在曲霉属中的流行情况各不相同,并且真菌病毒对其真菌宿主可能有不同影响:低毒力、高毒力或杀伤表型。在治疗方面,真菌病毒的细胞外传播至关重要。双链RNA真菌病毒缺乏细胞外阶段;然而,已描述了一种在曲霉基因组中有同源物的单链DNA真菌病毒具有细胞外传播模式。真菌病毒可诱导低毒力或杀伤表型,两者均可用于治疗。诱导低毒力的真菌病毒已被用于控制栗疫病,然而对于曲霉病,尚未鉴定出此类真菌病毒。真菌病毒编码的杀伤毒素或抗独特型抗体以及由此衍生的杀伤肽已被证明可控制包括动物曲霉病在内的真菌感染。这表明,只要鉴定出合适的真菌病毒,诱导这两种表型的真菌病毒均可用于治疗。