The Silent War of hMPV: Viral Interference with Host Immunity.

Human metapneumovirus (hMPV) is an important respiratory pathogen and a major cause of respiratory tract infections, particularly among vulnerable populations. Although hMPV was identified in 2001, it remains less extensively studied than other major respiratory viruses, such as influenza virus and respiratory syncytial virus (RSV), hindering the development of effective preventive and therapeutic strategies. This review examines the primary mechanisms by which hMPV evades host immune responses. The virus disrupts early innate immune signaling pathways, particularly those involved in the induction and signaling of antiviral interferons (IFNs) and modulates inflammatory responses. At the level of adaptive immunity, hMPV impairs T-cell activation and the development of long-lasting immunological memory, which may contribute to susceptibility to reinfection. The virus also alters the functions of several immune and structural cell types, including macrophages, dendritic cells, and respiratory epithelial cells. In addition, hMPV may modulate host microRNA expression to promote immune evasion and prolong infection. The recurrent nature of hMPV infections highlights the need to further investigate the immune-evasion mechanisms. Such research is essential for developing safer and more effective vaccines, antiviral agents, and immunomodulatory therapies.