Host factors in parainfluenza virus replication: from entry to innate immunity evasion.

Human parainfluenza viruses (HPIVs)are significant pathogens responsible for acute respiratory infections in infants, the elderly, and immunocompromised individuals. Among children under five, HPIVs are the second most common viral cause of acute lower respiratory tract infections (ALRIs), surpassed only by respiratory syncytial virus (RSV). Despite their significant health impact, there are currently no licensed vaccines or specific antiviral treatments for HPIV infection. Recent advances in functional genomics, including CRISPR-Cas9 screening, cDNA library screening, and multi-omics approaches, have enabled the systematic identification of host factors essential at different stages of HPIVs infections. This review aims to systematically summarize the latest evidence on host factors that influence viral entry, replication, assembly, and release, as well as those involved in evasion of innate immunity. Importantly, we contextualize the mechanisms of these host factors within the broader network of virus-host interactions. By integrating these insights, we aim to provide a strong mechanistic foundation for understanding HPIV pathogenesis to accelerate the development of innovative host-directed therapies(HDTs).