Viruses, are ubiquitous nano-parasites that infect a wide spectrum of hosts, ranging from humans to archaea, with bacterial viruses (phages) being the focus of this study. Significant efforts were previously made to study the mechanisms that take place during phage infection. Yet, the changes in cell-wall topography and viscoelasticity of the host during phage infection and terminal release were not explored. Here we used bio-force spectroscopy to measure in real-time and in-vivo the topography and viscoelastic properties of E. coli cells during T4-phage infection. Our results indicate that after one hour of T4 infection the outer-membrane of E. coli cells was highly perforated, exhibiting cavities of up to 350 nm in diameter. Within that first hour of T4 infection, mechanical measurements show that E. coli cells were structurally intact, yet significantly (1 fold) harder. During the second hour the E. coli cells were perforated and exhibit softer behavior 2-800 KPa, following complete cell lysis after 3 hours since the T4 infection. We suggest that during the first hour, host cells swell due to intercellular biosynthesis and assembly of new T4, thus rendering the E. coli cells to be more rigid. During the second hour, newly formed T4 burst out from numerous cavities in the E. coli cell-wall, following by cytoplasm release, resulting softer (more viscoelastic) cells. Shedding light on the structural and mechanical changes of biological cells following virus infection may introduce new opportunities to study this processes, and ultimately may inspire the development of novel antiviral solutions.