## 1 Introduction
In the last two decades, numerous transcriptome and proteome studies have provided a systematic understanding of secondary metabolite biosynthesis pathways and elucidated the role of structural and regulatory genes for bitter acids [6; 16; 17; 18; 19; 20; 21; 22], essential oils [23; 24; 25], and prenylated flavonoids [26; 27; 28; 29; 30; 31; 32] biosynthesis in hop. The high-throughput next-generation sequencing (NGS) technologies and computational biology tools allow to obtain rapid and cost-effective transcriptomic resources, providing better insight into viroid-hop plant interactions for understanding the host response to viroid infection [33; 34; 35]. The molecular mechanism of viroid-induced pathogenesis concerns the accumulated viroid-specific small RNAs (vd-sRNA) that are involved in transcriptional and post-transcriptional gene silencing via gene methylation and RNA interference (RNAi), and/or direct interaction with plant proteins [35]. In silico prediction of vd-sRNA targets found 1,062 unique targets for HLVd vd-sRNAs action [33]. Transcriptome analyses have shown the dynamic modulation of genes involved in protein, sugar metabolism, photosynthesis, physiology, phytohormone-signaling pathways, plant defense responses, and the cell wall structure. HLVd viroid infection has influenced an expression of plant resistance genes [33], transcription mediator genes [34], as well as transcription factors genes and secondary metabolites biosynthesis genes [35]. Changes of structural and regulatory genes for secondary metabolites biosynthesis were studied in leaves but the expression of these genes is the highest in lupulin glands inside hop cone. Proteosynthesis machinery includes the regulation of several processes connected to 5S rRNA biogenesis by the ribosomal protein L5 (RPL5) and transcription factor IIIA (TFIIIA). TFIIIA protein expression is controlled by alternative splicing of the exon containing the plant 5S rRNA mimic (PSSM) [36]. Recently, a splicing variant, specifically TFIIIA-7 ZF, was identified as essential for the replication of potato spindle tuber vivid (PSTVd) [37; 38; 39]. PSTVd modulates its expression through a direct interaction with RPL5, resulting in an optimized expression of TFIIIA-7 ZF. It was found that TFIIIA-7 ZF and RPL5 cloned from _Nicotiana benthamiana_ also bind to HSVd [39]. It is suggested that the RPL5/TFIIIA-7 ZF regulatory cascade is employed for replication by other viroids in the family _Pospiviroidae_; this was proved for AFCVd and CBCVd in infected tobacco plants. TFIIIA and RPL5 mRNA levels during the development of tobacco pollen are very low at late stages of mature and germinating pollen [40]. Viroid replication was depressed to lead to vivid elimination. HLVd is also non-transmissible via generative phases [41] and the RPL5/TFIIIA-7 ZF regulatory cascade can similarly regulate its replication. It was found that TFIIIA-7 ZF expression significantly influenced the tripartite Myb2/bHLH2/WDR1 [29] and bipartite WRKY1/WDR1 [30] complexes in _Nicotiana benthamiana_, activating hop chalcone synthases as well as O-methyltransferase transferase and WRKY promoters [40; 42]. These results suggest that TFIIIA-7 ZF has the potential to modulate or change the expression of secondary metabolite genes in hop upon vivid infection. In the present work, we aimed to evaluate the influence of HLVd infection on the content and composition of secondary metabolites in matureted hop cones. In parallel, we evaluated the expression levels of genes involved in secondary metabolites biosynthesis and regulation to provide a complex understanding of transcriptomic and metabolic changes caused by vivid infection.