The seven APOBEC3 proteins are cytidine deaminases, key antiviral innate immune effectors of the human proteome. They bind viral nucleic acid and catalyze C-to-U mutations. From the outbreak of SARS-CoV-2, and still to this day, the SARS-CoV-2 transcriptome is described as being shaped by host factors. Among them, APOBEC3-attributed mutagenesis is the most represented mutagenic bias. Despite some studies investigating the role of APOBEC3 proteins in SARS-CoV-2 replication, no consensus is available. We developed an infection model of immortalized normal human bronchial epithelial cells transduced with both ACE2 and TMPRSS2 lentiviral expressing constructs (HBEC3-KT-AT). HBEC3-KT-AT cells were infected with four different variants of concern (VOCs), namely, Wuhan, Alpha, Delta, and Omicron. Cellular RNA quantification shows that, with all VOCs, APOBEC3G mRNA expression is upregulated in a dose-dependent manner. Cellular protein quantification indicates that, with Wuhan, Alpha, and Omicron VOCs, APOBEC3G protein content is increased in a dose-dependent manner. Strikingly, infection with the Delta VOC does not trigger APOBEC3G protein increase. Experiments are needed to investigate the mechanism underlying the absence of correlation between APOBEC3G mRNA and protein content upon Delta VOC infection. Preliminary data suggest that, upon SARS-CoV-2 infection, APOBEC3G protein is associated with the nucleoprotein. These findings shed light on the interplay between APOBEC3 proteins and SARS-CoV-2 replication.