In order to investigate protein V binding partners and the cellular pathways modulated by protein V, affinity purification coupled with SILAC based quantitative proteomics was used to determine the viral and cellular protein(s) binding to adenovirus protein V. This analysis indicates that the viral protein IVa2 and three cellular proteins (C1QBP, KNPA4 and PARP1) may bind to adenovirus protein V. Furthermore, quantitative proteomics and RNAseq techniques were combined to examine the response of cellular proteins and genes in A549 and WI-38 cells infected by Ad5-dVrTSB compared to wild type Ad5 and rAd5-EGFP. Interestingly, I found that PARP1 and C1QBP were moderately increased by wild type Ad5 infection in both cell lines, but remained unchanged with Ad5-dVrTSB and rAd5-EGFP infection. Furthermore, PARP1 knockdown experiments indicated that PARP1 could make a small positive contribution to wild type Ad5 replication, but not for Ad5-dVrTSB replication. Finally, C1QBP knockdown experiments showed that C1QBP may play a role in inhibiting wild type Ad5 replication.