Influenza virus infections: clinical update, molecular biology, and therapeutic options

Abstract The viral family Orthomyxoviridae comprises five genera, but only two are of medical relevance in humans, namely: influenza A and B viruses. Influenza A viruses are further divided into subtypes, based on the antigenic properties of the surface glycoproteins hemagglutinin and neuraminidase. Influenza A virus is a single-stranded, enveloped RNA virus with 8 RNA segments. The initial target of Influenza A infection is the respiratory epithelium and the virus life cycle is initiated by the binding of viral HA to receptors on host cells, which triggers endocytosis of the virus. Once internalized, viral ribonucleoprotein complexes are released into the cytoplasm, transported to the nucleus, where viral replication occurs through the synthesis of new viral components which are transported to the plasma membrane, where the new viruses are formed and exit the infected cell. On average, influenza viruses infect 5–10% of human populations each year, but in some geographical areas or age groups these percentages can heavily increase, especially when a novel influenza virus finds a human population that lacks a suitable neutralizing immune response. We do not yet have an entire understanding of the elements and mechanisms that are fundamental for allowing influenza virus transmission, pandemics generation, and establishment of novel lineages. Influenza virus evolution and consequent pandemics is coarsely driven by two mechanisms: mutations in the viral genome, and reassortment, which is the rearrangement of the eight influenza A viral RNA segments in cells infected with at least two different viruses. Currently, infections due to influenza A virus are responsible for considerable morbidity and mortality worldwide and the loss of life and economic costs are awesome during annual influenza virus epidemics, and can be frightening during worldwide outbreaks of novel strains (pandemics). The present chapter will discuss molecular biology of influenza A viruses together with influenza infections clinical features and therapeutic options.