Updated project metadata. The control of host processes which influence cell-cell communication is central to determining the outcome of a virus infection in tissue. Despite this, it remains unclear how cells either in close or distant proximity to an infected cell differentially respond to the primary infection. Here, we established a virus infection microenvironment to resolve molecular features and functional consequences of cell spatial address within this localized niche by mass spectrometry. To rule out the possibility that neighboring cells are infected by the viral progeny from the primary infection, cidofovir is added in the system to prevent viral genome replication in order to prevent the spread of infection.