The Epstein-Barr virus (EBV) establishes lifelong B cell infection via oral transmission; however, it paradoxically drives carcinomas in anatomically distant organs with striking geographic disparities. While genomic studies frequently link specific EBV variants to these epithelial cancers, the mechanisms bridging ubiquitous infection to distant, strain-dependent malignancies remain largely unresolved. Using an induction-free primary B cell system, we identify a circulating B cell-vector pathway driving immortalized epithelial dissemination. We demonstrate that B cells infected with carcinoma-associated strains exhibit markedly higher epithelial transmission compared with those carrying lymphoid strains. This contact-dependent process requires spontaneous lytic reactivation, viral DNA replication, and de novo virion production. Crucially, those infected B cells retain their transmission capacity for months, supporting sustained epithelial seeding. Mechanistically, entry requires gH/gL engagement of EphA2/desmocollin-2 (DSC2), with actin- and PI3K-dependent endocytosis. These findings define a lytic-coupled, receptor-dependent pathway by which the EBV exploits B cells to access the epithelium, offering a mechanistic framework for understanding strain tropism and host-virus interactions.
While protein-protein interaction is the first step of the SARS-CoV-2 infection, recent comparative proteomic profiling enabled the identification of over 11,000 protein dynamics, thus providing a comprehensive reflection of the molecular mechanisms underlying the cellular system in response to viral infection. Here we summarize and rationalize the results obtained by various mass spectrometry (MS)-based proteomic approaches applied to the functional characterization of proteins and pathways associated with SARS-CoV-2-mediated infections in humans. Comparative analysis of cell-lines versus tissue samples indicates that our knowledge in proteome profile alternation in response to SARS-CoV-2 infection is still incomplete and the tissue-specific response to SARS-CoV-2 infection can probably not be recapitulated efficiently by in vitro experiments. However, regardless of the viral infection period, sample types, and experimental strategies, a thorough cross-comparison of the recently published proteome, phosphoproteome, and interactome datasets led to the identification of a common set of proteins and kinases associated with PI3K-Akt, EGFR, MAPK, Rap1, and AMPK signaling pathways. Ephrin receptor A2 (EPHA2) was identified by 11 studies including all proteomic platforms, suggesting it as a potential future target for SARS-CoV-2 infection mechanisms and the development of new therapeutic strategies. We further discuss the potentials of future proteomics strategies for identifying prognostic SARS-CoV-2 responsive age-, gender-dependent, tissue-specific protein targets.