Breaking barriers: Respiratory viral strategies targeting the host's nuclear pore complex and nuclear transport pathways.

From stealthy infiltrators to blunt-force saboteurs, many human viruses--perhaps all-disrupt nuclear transport to control host gene expression, suppress immune responses, and redirect cellular resources toward their own replication. Among them, respiratory viruses stand out for their global impact and relentless evolution, from seasonal scourges to pandemic threats. Focusing on adenoviruses, influenza, rhinoviruses, RSV, and SARS-CoV-2, we explore a series of molecular case studies that reveal both shared strategies and the diverse molecular innovations these respiratory pathogens use to subvert the nuclear transport machinery. We organize these tactics into six recurring strategies: NPC docking and nuclear entry, inhibition of immune-factor import, hijacking nuclear protein transport and karyopherins, sabotage of host mRNA export, degradation of FG-Nups, and exploitation of mitotic nuclear envelope breakdown. These insights not only illuminate fundamental virus-host conflicts but may also point the way toward new therapeutic vulnerabilities in the viruses' attack strategies.