Influenza virus research in an era of emerging respiratory threats: host–virus interactions, surveillance technologies, antiviral management and resistance, and vaccine preparedness

Abstract

Seasonal epidemics, zoonotic spillover, antiviral resistance, and pandemic risk continue to make influenza a major challenge for respiratory preparedness. The recent spread of highly pathogenic avian influenza A(H5N1) in mammalian hosts has made it increasingly important to consider molecular adaptation, surveillance, treatment, and vaccination as connected parts of preparedness rather than as separate issues. This review focuses on four interconnected areas: host–virus interactions, surveillance technologies, antiviral management and resistance, and vaccine preparedness. Evidence on mammalian adaptation includes receptor specificity, viral polymerase–host factor compatibility, innate immune antagonism, ANP32 proteins, and aberrant viral RNA generation, while surveillance has expanded to multiplex and CRISPR-based assays, point-of-care platforms, genomic sequencing, artificial intelligence-assisted risk assessment, and environmental monitoring. These approaches differ in intended use and stage of validation. Antiviral benefit depends strongly on host risk and treatment timing. Resistance-associated substitutions, however, cannot be interpreted from sequence data alone and require phenotypic and epidemiological context. Vaccine development spans nanoparticle, mRNA, and intranasal platforms designed to broaden antigenic coverage, strengthen mucosal immunity, or improve protection in specific populations. Better analytical performance and stronger immune responses do not by themselves demonstrate reductions in severe disease, hospitalization, or mortality. Influenza preparedness ultimately depends on how effectively these four domains inform one another and how consistently emerging approaches are evaluated against clinically meaningful outcomes.