Human Influenza Virus Infections

Abstract

Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection.

Fig. 1

A schematic representation showing major events involved in emergence of an influenza pandemic, from the two major animal reservoirs to the global outbreak in humans. Evolution steps of emerging strains are attentively followed by World Health Organization and classified into six stages.

Fig. 2

Key players in influenza A virus (IAV)-induced lung injury. While upper respiratory tract infection results in mild symptomatic IAV infection, severe cases of IAV usually involve spread of the virus to the lower respiratory tract. Here, resident alveolar macrophages (AM) and dendritic cells (DC) sense IAV infection of alveolar epithelial type I (AEC I) and type II (AEC II) cells. Cytokine release and establishment of a proinflammatory milieu in the alveolar lumen lead to recruitment of additional monocyte-derived macrophages (MDM) as well as neutrophils from the blood vessels to the site of infection. DC migration to the lymph nodes further induces generation of antigen-specific T cells into the vessel. An exuberant immune response with massive release of proinflammatory and proapoptotic mediators contributes to IAV-induced lung injury.