Influenza virus, belonging to the family of Orthomyxoviridae, is one of the most serious zoonotic pathogens and causes seasonal epidemics or periodic pandemics among human beings around the world. The viral envelope consists of a lipid bilayer derived from cells that anchors three of viral transmembrane proteins, hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). Influenza virus infection is initiated by the attachment of HA on virus particles to cell surface receptors containing sialic acids [12] . It has been known that the specific interaction between HA and sialic acid species is one of the determinants of the host range of influenza viruses [13] . Beside its role in the viral attachment, HA is also involved in intracellular fusion between viral envelope and host cell endosome membrane in the endocytotic pathway, by which the virus content is released inside the host cell [14] . The functional maturation of HA is mediated by the cleavage of HA into two disulfide-linked glycopolypeptides, HA1 and HA2 [15] , accomplished by trypsin or trypsin-like proteases derived from host cells [16] [17] [18] [19] . The membrane fusion is induced by a conformational change in the mature HA, which is triggered at low pH in the endosome, allowing viral ribonucleoprotein complexes to release into the cytoplasm [20, 21] . Thus, HA plays a critical role in initiation and progression of influenza virus infection. Influenza virus NA possesses the enzymatic activity that cleaves a-ketosidic linkages between terminal sialic acids and adjacent sugar residues of cellular glycoconjugates [22] . The sialidase activity of NA removes terminal sialic acid residues from HA and NA proteins as well as host cell surface glycoproteins. Since the terminal sialic acid of sialyloligosaccharides is critical for HA binding, the receptordestroying activity of NA serves to counter the receptor-binding activity of HA. It is quite likely that this activity contributes to prevention of successive superinfection of an infected cell [23] . In the absence of the functional sialidase activity, progeny virions aggregate on the cell surface due to the HA receptor-binding activity and can not be released [24, 25] . Thus, NA cleaves sialic acids from the cell surface and facilitates virus release from infected cells. However, it is not clear whether every progeny virion is released as cell-free virion to infect the uninfected cells after diffusion into the extracellular environment. Influenza viruses are generally transmitted as cell-free viruses from infected to uninfected cell but they may also infect through the cell-to-cell transmission, in particular during local lesion formation.