Not AvailableThe highly pathogenic avian influenza viruses (HPAIVs) cause severe disease in gallinaceous poultry species, domestic ducks, various aquatic and terrestrial wild bird species as well as humans. The outcome of the disease is determined by complex interactions of multiple components of the host, the virus, and the environment. While the host-innate immune response plays an important role for clearance of infection, excessive inflammatory immune response (cytokine storm) may contribute to morbidity and mortality of the host. Therefore, innate immunity response in avian influenza infection has two distinct roles. However, the viral pathogenic mechanism varies widely in different avian species, which are not completely understood. In this review, we summarized the current understanding and gaps in host-pathogen interaction of avian influenza infection in birds. In first part of this article, we summarized influenza viral pathogenesis of gallinaceous and non-gallinaceous avian species. Then we discussed innate immune response against influenza infection, cytokine storm, differential host immune responses against different pathotypes, and response in different avian species. Finally, we reviewed the systems biology approach to study host-pathogen interaction in avian species for better characterization of molecular pathogenesis of the disease. Wild aquatic birds act as natural reservoir of AIVs. Better understanding of host-pathogen interaction in natural reservoir is fundamental to understand the properties of AIV infection and development of improved vaccine and therapeutic strategies against influenza.Not Availabl