The tropism in an infected animal body is generally restricted to respiratory tract or lung and its periphery, and the requirement of a trypsin-like protease has been generally described for the reason of the restriction. It is possible that the cell-to-cell transmission mode may play a significant role for the virus spreading inside of organism, although cell-free influenza virions are causative of highspeed spreading. At the least, the limited but distinct level of infection followed by replication could provide some opportunity to generate influenza virus variants. It is an open question whether the cell-to-cell transmission mode is involved in the pathogenesis caused by influenza virus infection in vivo.