Time-resolved proteomics of Adenovirus infected cells

ABSTRACT: To combat virus infections, which are major human killers, a deeper understanding of how viruses reprogram their hosts to create optimal production of progeny is needed. Most knowledge on the regulation of cellular gene expression during adenovirus infection is derived from studies of mRNA expression. Here, we investigated the changes in cellular protein expression during the early phase of adenovirus type 2 (Ad2) infection of primary human cells by stable isotope labeling in cell culture (SILAC) with subsequent liquid chromatography-high resolution tandem mass spectrometric (LC-MS/MS) analysis using a Q-Exactive Orbitrap instrument. Cells were in-depth evaluated 6 and 12 hours post infection (hpi) and two biological replicates were investigated using swapped labeling. In total, 2027 and 2150 proteins were quantified at 6 and 12 hpi, respectively. Among them, 431 and 544 were deregulated more than 1.5-fold at the two time points. For the deregulated proteins the change in protein expression was compared with that of late phase of infection (see PXD004095). Pathway analysis showed that De novo purine and pyrimidine biosynthesis, Glycolysis and Cytoskeletal regulation by Rho GTPase pathways are activated early during the infection, while the inactivation of the Integrin signalling pathway starts between 6 and 12 hpi. The transcription factor MYC was predicted to be activated with time, and the phosphopeptide analysis revealed the up-regulation of phosphosites related with glycolysis or cytoskeletal reorganization. These results complement the previous knowledge obtained from transcriptomic data, and show novel and specific aspects of how adenovirus influence host cell gene expression at the protein level.The results contribute to our understanding of host cell gene regulation during infection at a deeper level.

INSTRUMENT(S):

ORGANISM(S): Human Adenovirus C Serotype 2 (hadv-2) (human Adenovirus 2) Homo Sapiens (human)

TISSUE(S): Fibroblast Of Lung, Cell Culture

DISEASE(S): Viral Infectious Disease

SUBMITTER: Sara Lind  

LAB HEAD: Sara Lind

PROVIDER: PXD008980 | Pride | 2018-10-04

REPOSITORIES: Pride