Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection

Highly pathogenic human coronaviruses, including SARS-CoV, SARS-CoV-2, and MERS-CoV have emerged as significant public health threats due to their ability to cause widespread outbreaks and pandemics. These viruses induce dysregulated inflammatory responses, typified by cytokine storms that drive extensive tissue damage in pulmonary and extrapulmonary systems, leading to acute respiratory distress syndrome (ARDS) and multi-organ failure. These pathological outcomes are driven by sophisticated mechanisms that manipulate host immune pathways and evade innate and adaptive immune surveillance. The innate immune system plays a pivotal role in the early detection and control of viral infections through mechanisms such as cytoplasmic RNA sensors, Toll-like receptors, interferon signaling, and inflammasome activation. However, these coronaviruses effectively exploit and subvert these processes, suppressing antiviral defenses while amplifying inflammatory cascades. This review delineates the molecular and cellular strategies employed by these pathogens to evade immune recognition and exacerbate immune-mediated tissue injury. Understanding these processes is fundamental for guiding the development of targeted antiviral interventions, immunomodulatory therapeutics, and robust strategies to mitigate the impact of future coronavirus pandemics.