Background: Direct transmission of avian influenza viruses with human receptor binding specificity to humans is a serious risk of newly emerging virus responsible for pandemy. The analysis of recent avian influenza hemagglutinin sequences and their glycans show their affinities to the human sialic acid receptors. The upregulation of proinflammatory cytokines and type I IFN genes, and host cell death responses contribute to the pathogenesis of influenza infection. Understanding the host cell-virus interactions and replication dynamic of the viruses in different cells is an essential step in surveillance and controlling programs against influenza.