Naming influenza viruses
The influenza virus belongs to the family Orthomyxoviridae, of which there are three types, designated influenza A, B and C (two other members of this family, the Dhori and Thorgoto viruses are borne by ticks and are rarely encountered). Influenza A viruses (which include the avian or bird viruses) cause the most severe disease in humans, although influenza B regularly causes outbreaks. In winter 2005 in the southern hemisphere, there was a serious influenza B outbreak in New Zealand.
The A, B and C designations originally referred to broad classes of antibody response to the virus and are now known also to be related to genetic differences in the respective M1 (capsid or matrix protein) or the nucleoprotein (NP) of the three virus types (see the Influenza Primer II for more about these components of the influenza virus). Studies of the genetic sequences of these viruses indicate that at some time they all had a common ancestor. The H5N1 bird flu virus belongs to the influenza A class or type.
The type (A, B or C) is the first important part of the influenza virus name. Then comes the sub-type, which is named for the broad classes of the hemagglutinin (HA) or neuraminidase (NA) surface proteins sticking through the viral envelope. There are 16 HA sub-types (designated H1 - H16) and 9 NA sub-types (designated N1 - N9). All of the possible combinations of these influenza A subtypes infect birds, but only those containing the H1, H2, H3, H5, H7 and H9 and the N1, N2 and N7 surface proteins infect humans, and of these, so far, only H1, H2, H3 and N1 and N2 do so to any extent. The H5 subtype is considered a candidate for a new subtype for broad human infectivity. Since this subtype is “new” to the immune systems of most people on the globe, if this happens it is likely to be in pandemic form, that is to produce a wave of infection around the world. Full naming of an influenza A virus thus includes both the type and the subtype (e.g., influenza A/H5N1 or influenza A/H3N2; these may also be written using parentheses instead of slashes, i.e. A(H3N2) etc.).
However finer distinctions are also necessary because influenza viruses mutate readily and within subtypes there may be many genetic variants, called strains. When a sample of a virus is taken and grown in culture it is called an isolate. The particular laboratory’s serial number or isolate code (which is arbitrary and specific for each laboratory), the animal the isolate was taken from, its location and the year become part of the strain designation. Thus in the full name of an influenza A virus we have: A/location/isolate number/year. Currently the specific animal species is included as well.
The paper in Nature of July 6, 2005 that compared the H5N1 virus from the migratory bird die-off in Qinghai China to H5N1 viruses elsewhere named the virus in this way: A/Bar-headed Gs/QH/12/05(H5N1). In other words, it was an influenza A type from a Bar-headed Goose in Qinghai (QH), isolate number 12 from the laboratory, taken in 2005. Sequencing of two of the 10 proteins showed the virus to be closely related to another H5N1 virus, A/Chicken/Shantou/4231/2003. Thus there is some variation in the naming, as in this case, where the year is given as 2005 instead of 05 and the H5N1 is omitted because it is clear from the context of the paper that this was the subtype.
Sometimes a shorthand designation is used when it is clear what is meant or some of the elements are not relevant or where historical use omits them. For example, the virus isolated by William Smith in 1933 that was adapted to nervous tissue is usually abbreviated WSN/33 or WSN/33(H1N1), for William Smith (Neurotropic) virus. Often the first time a strain is mentioned in a paper it is given a full designation and then abbreviated in an obvious manner. An example comes from the paper by Kobasa et al. where A/Memphis/8/88(H3N2) (i.e., influenza A, isolate labeled 8 from Memphis in 1988) is afterward referred to simply as M88.
Finally, the influenza A/H5N1 virus, because of its special importance in recent years, has received yet another refinement, its “genotype.” A virus’s genotype can refer to its specific genetic sequence, or, as in this case, to a broad class of genetic sequences based on the various combinations of the eight separate gene segments the strain contains. Using as a basis the H and N genes of the original 1996 isolate from a goose in Guandong province in southern China (thus Goose/Guangdong/1/96 or Gs/GD-like lineage), different classes of genotype based on the six other (internal) genes were designated according to the combinations produced by reassortments with other subtypes (see Influenza Primer II). In 2001 six reassortant types were known (genotypes A, B, C, D, E and X0), all from poultry. Beginning in 2002 eight new genotypes were found, designated V, W, X1, X2, X3, Y, Z and Z+, replacing the previous genotypes (A - E) from Gs/Gd. Except for the X0 - X3 genotypes, all of the new ones had a mutation in one of the internal proteins (NS) that involved a five amino acid deletion in positions 80 - 84. In addition, all genotypes except for B, W and Z+ had a 20 amino acid deletion in the NA protein (positions 49 - 68), as in the Qinghai virus. Genotype Z has the 20 amino acid deletion but Z+ does not, so the Qinghai virus is designated a genotype Z virus. Genotype Z is now the dominant genotype in Indonesia, Thailand, Vietnam and southern China.