Our findings showed that the NA-deficient influenza virus is not diffused into the extracellular environment. The viral spreading in the absence of oseltamivir appears to be much faster compared to the viral spreading in the presence of the drug, suggesting that NA could be involved in determination of spreading speed ( Figure 4B ). The NA activity prevented progeny virions from entering cells which virus came from (Figure 6 ), implying that progeny virus particles should be transmitted to adjacent uninfected cells. The cell-to-cell transmission started in early phase of infection, and the virus spread through diffusion of cell-free viruses ( Figure 4B ). Indeed, it was reported that the cell-to-cell transmission is a rapid spreading pathway in the case of vaccinia virus [3] . Vaccinia virus induces a blocking mechanism of superinfection and thereby infects to adjacent uninfected cells efficiently. In early phases of vaccinia virus infection, viral proteins A33 and A36 are expressed at the infected cell surface. Once cell-free virus particles contact the filopodium, the A33/A36 complex induces the formation of actin filament, which causes this superinfected virion to be repelled toward uninfected cells [3] . Influenza viruses can re-infect the cells previously infected in the presence of oseltamivir (Figure 6 ), suggesting that a progeny virion may be bridged by HA between infected and adjacent uninfected cells temporarily. Thus, in the case of the cell-to-cell transmission of influenza virus, we propose that progeny virions associated with the surface of infected cells even after budding are directed to adjacent uninfected cells. The cell-to-cell transmission mechanism of influenza virus is distinctly different from that of vaccinia virus in the infecting virus status: Infected cell-associated virions and cell-free virions are involved in the cell-to-cell transmission of influenza virus and vaccinia virus, respectively. The strategy for influenza virus appears to be similar to that for HCV. HCV progeny virions budded from an infected cell are trapped between infected and uninfected adjacent cell membranes at the tight junction. HCV virions then, enter into adjacent cells through endocytosis and low pH-dependent membrane fusion using Claudin-1 [8] . The cell-to-cell transmission of influenza virus also required functional HA and endosome acidification by M2 ion channel. However, it has not been reported that HCV has a gene encoding a receptor destroying enzyme similar to NA of influenza virus. We speculated that HCV progeny particles are bridged between infected and adjacent uninfected cells temporarily like influenza virus in the presence of oseltamivir. Progeny influenza virus particles could be transmitted to adjacent uninfected cells efficiently in the presence of the NA activity, suggesting that the cell-to-cell transmission of influenza virus is more strategic than that of HCV.