Vaccines can only temporarily control the recurring epidemics of influenza, because antigenic changes are typical for HA and NA. This goes along with adaptation to small molecule inhibitors (e.g. Development of therapeutic antibodies against influenza is a challenge, as the high viral mutation rate (antigenic drift) and genetic reassortment of the virus genome (antigenic shift) continuously lead to new strains escaping from neutralization by antibodies. In diagnostics, antibodies against spike proteins are the preferred tool for identification and serotyping of viruses. NA cleaves glycosidic bonds with terminal SA facilitating the release of budding virions from the cell. It mediates attachment to the host cell surface via binding to sialic acid (SA) residues of cellular receptors, and upon endocytic virus uptake it triggers fusion of the envelope with the endosomal membrane releasing the viral genome into the cytoplasm. The homotrimeric HA is the most abundant protein on the viral surface. The envelope bilayer harbors the two spike glycoproteins hemagglutinin (HA) and neuraminidase (NA), and the M2 proton channel. The genome of influenza virus consists of eight segmented negative RNA strands. In 2009 the pandemic swine origin influenza A H1N1 virus as well as the outbreak of H7N9 in China in 2013 has reminded the world of the threat of pandemic influenza.
The Spanish flu pandemic of 1918 as well as the Asian flu of 1957 and the Hongkong flu in 1968 pandemics caused the death of millions of people. It can cause annual epidemics and infrequent pandemics. Influenza A virus is an enveloped virus belonging to the Orthomyxoviridae family.