Influenza Virus

Influenza viruses are members of the family Orthomyxoviridae. This family represents enveloped viruses the genome of which consists of segmented negative-sense single-strand RNA segments. There are four genera of this family: types A, B, C and Thogotovirus, of which, however, only genera A and B are clinically relevant for humans. The eight genome segments of influenza A and B viruses are loosely encapsidated by the nucleoprotein. The polymerase complexes consisting of the three polymerase proteins PB1, PB2, and PA are located at the ends of the nucleocapsids. These helical capsids are encircled by the M1 matrix protein and by a host-derived lipid bilayer envelope in which the virus surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) as well as the M2 matrix protein are embedded [1]. The HA is synthesized as precursor protein and cleaved by cellular serine proteases into the functional proteins HA1 and HA2. The amino acid sequence at the cleavage site determines HA processing by cellular proteases and thus, also the organ tropism. Mutations at the cleavage site of avian influenza viruses may lead to an insertion of alkaline amino acids. Ubiquitous proteases such as furin can cleave such a mutated HA and, as a consequence, permit systemic spreading of the virus. This mechanism changes a lowly pathogenic into a highly pathogenic avian influenza virus and has been associated so far only with subtype H5 and H7 viruses. Influenza virus as an enveloped virus is relatively vulnerable to damaging environmental impacts. Depending on environmental conditions (e.g. humidity and temperature), however, it can survive up to several hours and in water at low temperatures (e.g. <20 °C) also considerably longer (up to several months). Influenza viruses are sensitive to lipid solvents and detergents. They are also vulnerable to heat and a low pH, depending on the virus type. Influenza A viruses with uncleaved HA are obviously more stable (loss of infectivity at pH <4.5) than viruses with cleaved HA (loss of infectivity at pH <5) [2]. The most outstanding characteristic of influenza viruses is their rapid evolution which leads to its great variability. This is the case especially with influenza A viruses. According to the antigenic properties of their envelope proteins, influenza A viruses are subdivided into a number of subtypes. 16 different HA and 9 different NA subtypes have been identified so far. The nomenclature system follows the pattern H(x)N(y) including the host of origin, geographical location, strain number, and year of isolation [1, 3]. Influenza B viruses are not further divided into subtypes. The accumulation of point mutations leads to a step-by-step modification of the virus proteins (above all in the two surface antigens HA and NA). This mechanism is described as ‘antigen drift’ and is also typical of influenza B viruses. The variability of the type B viruses, however, is also characterised by other mechanisms such as insertion and deletion, as the influenza B lines show which have been co-circulating and stable for more than 20 years [4, 5]. The process of ‘antigen shift’ (re-assortment) is defined as the exchange of whole genome segments, above all HA genes, which might result in influenza viruses which have a selective advantage compared with their parent viruses. A prerequisite for this re-assortment is simultaneous infection of a cell by two different influenza A viruses. This will result in a variety of different hybrid viruses with different characteristics which they have received from the parent viruses via the individual genome segments. An example is the occurrence of the influenza A/H2N2 subtype in 1957 which superseded the influenza A/H1N1 virus which was dominant until then [6, 7]. Special attention was drawn to the public by the deaths caused in humans by the highly pathogenic avian influenza A/H5N1 subtype. These cases have shown that an entirely new influenza A virus can cause deadly infections in humans. Since the first outbreaks of H5N1-related avian influenza in poultry in South-East Asia in 2003, human H5N1 transmissions with Clinical Information · Klinische Information