Abstract Simple Summary In this study, an integrated analysis of the mRNA and protein was performed to identify important putative regulators involved in the transmission of CMV (cucumber mosaic virus) by aphids. At the level of transcription, a total of 20,550 genes (≥2-fold expression difference) were identified as being differentially expressed genes (DEGs) 24 h after healthy aphid transfer to infected tobacco plants using the RNA-seq approach. At the protein level, 744 proteins were classified as being differentially abundant between virus-treated and control Myzus persicae using iTRAQ (isobaric tags for relative and absolute quantitation) analysis. The combined mRNA and protein analysis enabled the identification of some viral putative regulators, such as cuticle proteins, ribosomal proteins, and cytochrome P450 enzymes. The results show that most of the key putative regulators were highly accumulated at the protein level. Based on those findings, we can speculate that the process by which aphids spread CMV is mainly related to post-translational regulation rather than transcription. Abstract Aphids transmit CMV (cucumber mosaic virus) in a non-persistent manner. However, little is known about the mechanism of CMV transmission. In this study, an integrated analysis of the mRNA and protein was performed to identify important putative regulators involved in the transmission of CMV by aphids. At the level of transcription, a total of 20,550 genes (≥2-fold expression difference) were identified as being differentially expressed genes (DEGs) 24 h after healthy aphid transfer to infected tobacco plants using the RNA-seq approach. At the protein level, 744 proteins were classified as being differentially abundant between virus-treated and control M. persicae using iTRAQ (isobaric tags for relative and absolute quantitation) analysis. The combined mRNA and protein analysis enabled the identification of some viral putative regulators, such as cuticle proteins, ribosomal proteins, and cytochrome P450 enzymes. The results show that most of the key putative regulators were highly accumulated at the protein level. Based on those findings, we can speculate that the process by which aphids spread CMV is mainly related to post-translational regulation rather than transcription. Keywords: cucumber mosaic virus (CMV), iTRAQ, Myzus persicae, transcriptome 1. Introduction The green peach aphid, Myzus persicae (Sulzer) (Homoptera: Aphididae), is one of the most important agricultural pests worldwide [[34]1]. Aphids have a wide host range, exceeding 400 plant species from 40 different plant families, and can cause severe yield losses in agricultural production systems [[35]2]. In addition to sucking phloem sap, aphids are also vectors for the transmission of more than 200 different plant viruses [[36]1,[37]3]. In general, aphids live on different hosts in the winter and in the summer. Aphids exhibit parthenogenetic reproduction in some conditions, so they can reproduce on the same host in all seasons, and the harm caused by aphids is enduring. Due to the parthenogenetic reproduction of their hosts, plant viruses spread by aphids may cause outbreaks that can lead to significant crop losses. In addition, plant virus also can affect behavior of aphid vectors. Peñaflor et al. found the population growth of Aphis glycine was reduced and the probing preferences was increased