Human respiratory syncytial virus (HRSV) is a leading cause of virus-induced paediatric respiratory disease. HRSV can cause severe lower respiratory tract diseases in young children and upper respiratory tract diseases in all ages. HRSV infection results in large economical and healthcare burdens every year, however, there is no approved vaccine and the antiviral therapies are generally costly and less effective due to the high mutant rate of this RNA virus and the imbalanced host immune responses in response to HRSV infection. The virus-host interactions of HRSV have not been well understood so far, which therefore limited the knowledge of HRSV pathogenesis and the development of vaccinations and antiviral drugs. This study focused on investigations of the interactions between HRSV and host NF-KB activation and host cell cycle manipulation, as well as the interactions between HRSV nonstructural proteins and host cellular proteins. In conclusion, different NF-KB activation characteristics have been found between HRSV subgroups A and B, suggesting the implication with the different pathology of HRSV subgroup A and B. HRSV infection resulted in cell cycle arrest at GO/G1 phase with different mechanism in continuous and primary cell cultures, which benefited progeny virus production. HRSV NS1 protein was found to act as a role in HRSV induced cell cycle arrest, and a potential inhibitor of RNA polymerase". All of these findings provided a better understanding of HRSV virus-host interactions and HRSV pathogenesis.