Respiratory Viruses and Pulmonary Diseases: Mechanisms, Therapies, and Metabolic Reprogramming.

Abstract

Respiratory viral infections constitute a substantial global health challenge, extending their impact beyond acute inflammation to encompass long-term pulmonary sequelae. Recent evidence highlights that respiratory viruses such as influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 reprogram host metabolism to facilitate their replication, with significant alterations in glucose metabolism playing a critical role. This metabolic reprogramming augments glucose metabolism via activation of core signaling pathways including PI3K/Akt/mTOR, HIF-1α, and c-Myc. Beyond facilitating viral proliferation, these metabolic changes crosstalk with oncogenic signaling. By triggering chronic inflammation, oxidative stress and genomic damage, they disrupt the pulmonary immune microenvironment and ultimately promote the pathogenesis of lung cancer and chronic obstructive pulmonary disease (COPD). The pathogenesis of these symptoms is multifactorial and is influenced by genetic susceptibility, environmental exposure, and key interactions between persistent viral infection and the host's immune system. In this review, we synthesize recent advancements on the molecular mechanisms linking virus-induced metabolic alterations to the progression of pulmonary diseases. Furthermore, we discuss novel therapeutic strategies aimed at targeting these metabolic vulnerabilities to mitigate the long-term risks associated with respiratory infections.