Autophagy and Respiratory Viruses: Mechanisms, Viral Exploitation, and Therapeutic Insights.

Respiratory viruses, such as influenza virus, rhinovirus, coronavirus, and respiratory syncytial virus (RSV), continue to impose a heavy global health burden. Despite existing vaccination programs, these infections remain leading causes of morbidity and mortality, especially among vulnerable populations like children, older adults, and immunocompromised individuals. However, the current therapeutic options for respiratory viral infections are often limited to supportive care, underscoring the need for novel treatment strategies. Autophagy, particularly macroautophagy, has emerged as a fundamental cellular process in the host response to respiratory viral infections. This process not only supports cellular homeostasis by degrading damaged organelles and pathogens but also enables xenophagy, which selectively targets viral particles for degradation and enhances cellular defense. However, viruses have evolved mechanisms to manipulate the autophagy pathways, using them to evade immune detection and promote viral replication. This review examines the dual role of autophagy in viral manipulation and host defense, focusing on the complex interplay between respiratory viruses and autophagy-related pathways. By elucidating these mechanisms, we aim to highlight the therapeutic potential of targeting autophagy to enhance antiviral responses, offering promising directions for the development of effective treatments against respiratory viral infections.