Editorial: Viral pathogenesis and host defense: understanding the missing links to combat disease

Viral diseases remain among the most complex biological challenges of the present time, not simply because viruses replicate rapidly, but because they exploit core cellular pathways and reshape host biology. The true burden of infection lies in the "missing links" connecting viral entry to immune disruption, cellular hijacking to systemic pathology, and acute illness to longterm consequences (V'kovski et al., 2021). To combat disease effectively, the field must move beyond description toward a mechanistic understanding of host vulnerability and resilience, including the balance between protective antiviral immunity and harmful immunopathology (Blanco-Melo et al., 2020;Sette and Crotty, 2021) Together, these studies highlight that host defense is not only about mounting a response, but about restoring immune equilibrium after infection, a critical gap that future therapies must address. Taken all together, these studiesarticles in this research topic illuminate viral pathogenesis as a multi-layered process: beginning with entry, shaped by metabolism, amplified through immune evasion, and extending into prolonged immune disruption and systemic consequences (Figure 1). They redefine host defense as more than an acute response, instead reflecting a longterm balance of immune restoration, regulatory control, and translational readiness. In this context, clarifying how viral mechanisms translate into host immune and clinical outcomes is essential for combating disease effectively. The future of antiviral therapeutics will depend on integrating mechanistic precision with clinical relevance, transforming fundamental insights into interventions that strengthen host resilience as much as they target viral vulnerability.Taquet, M., Sillett, R., Zhu, L., Mendel, J., Camplisson, I., Dercon, Q., et al. (2022).Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients. Lancet Psychiatry 9, 815-827. doi: 10.1016/S2215-0366( 22)00260-7V'kovski, P., Kratzel, A., Steiner, S., Stalder, H., and Thiel, V. (2021). Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol 19, 155-170. doi: 10.1038/s41579-020-00468-6