Quantitative proteomic analysis of A549 cells infected with human adenovirus type 2

Abstract

Human adenovirus (HAdV-2) is considered a common agent of respiratory tract infection in the human, especially in children. Virus infection is believed to modify host cell expression necessary for its replication and therefore cell proteome can reflect the changes of specific cellular pathways during infection. This study aims to identify differentially expressed proteins of A549 cells in response to HAdV-2 infection using a label-free liquid chromatography-high-resolution tandem mass spectrometry strategy (LC-MS/MS) at 24 and 48 hpi. A total of 248 and 216 proteins were deregulated by 1.35-fold at 24 and 48 hpi, respectively. Among them, 155 were upregulated at 24 hpi and 86 at 48 hpi, whereas 93 and 130 were downregulated at 24 and 48 hpi, respectively. The identified proteins were involved in different pathways as energy, transcription, protein synthesis, cytoskeleton, rescue and defense, cell cycle, DNA processing, transportation, and metabolism. Glycolytic pathway and histone deregulated proteins were further confirmed by chemical testing and immunofluorescence, respectively. The results suggest that the identified proteins influenced HAdV-2 infection in the context of viral replication and propagation. This study complement proteomic data obtained from previous studies and reinforce the understanding of the relationship between HAdV and host cell. Highlights• HAdV-2 affects the expression of different cellular pathways to control the host cell.• The virus use the glycolysis pathway as a source of energy during infection.• The consumption of high levels of glucose accompanied by the production of lactate was observed to generate the required energy. K E Y W O R D S A549 cells, deregulated proteins, glucose utilization, human adenovirus (HAdV-2), liquid chromatography/mass spectrometry (LC-MS)

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“…The major forms, the 289 residue (R) and the 243R proteins (resulting from the 13S and 12S mRNAs, respectively), interact with a variety of cellular proteins including cell cycle regulators, epigenetic regulators and transcription factors [ 5 , 6 , 42 , 43 , 44 , 45 , 46 ]. These interactions, among other functions, serve to enhance viral gene expression, alter the cellular gene expression profile, modulate the function of host proteins, and induce mitogenic activity within the host cell to promote a productive infection [ 9 , 37 , 47 , 48 , 49 ]. The 55 kDa protein product from the E1B region has been implicated in the ubiquitination of cellular proteins (e.g., p53), the inactivation of cellular DNA damage response and the regulation of viral mRNA export [ 50 , 51 ].…”

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“…. Therefore, many studies have been carried out to study its relationship with the host cell (Guissoni et al 2018;Badr et al 2019), and on the other hand evaluate its prevalence within the community (Öner et al 2022) or in the environment (Quintão et al 2021).…”