7.1 Phylogenetic diversity and nomenclature for measles genotypes

Mick Mulders

A uniform method to describe the genetic diversity of wild-type measles viruses was adopted in 1998, following a meeting of experts hosted by WHO [13]. The published report of the meeting provided the recommended protocols for sequencing and phylogenetic analysis and included reference measles strains for each of the 15 genotypes that had been characterized at that time. The genotypes were assigned to one of the 8 major clades (A-H) according to phylogenetic analyses of the 450 nucleotides that code for the carboxyl-terminal 150 amino acids of the nucleoprotein (N-450). Clade A includes all vaccine strains of measles virus. Subsequent reports specified the requirements for a new genotype including the minimum nucleotide divergence from recognized genotypes. Each update of the nomenclature for measles genotypes has provided the status of known genotypes, along with the designated reference strain(s) [14-19].

The number of clades that have been identified and described has remained unchanged since 1998, however the number of genotypes within a clade has increased, particularly within clade D. Wild-type viruses in clade A are considered to be extinct. As of the 2015 update [19], 24 measles genotypes have been recognized. Clades A, E and F have continued to consist of only a single genotype. All of the recognized genotypes have one reference strain, except for B3, C2, D5 and D7, which have two reference strains. During 2005-2015, 11 wild-type genotypes were detected, and in 2017 only five genotypes in three clades (B3, D4, D8, D9, and H1) were detected/reported to MeaNS. Refer to Figure 7.1, Circulation of measles viruses 2005-2017.

The letter designation of the clade is used when referring to a genotype if it is the only member of a clade (e.g., genotype A). In 2001, when an additional genotype was recognized within clade H, the original viruses comprising genotype H were grouped together as genotype H1 and the new genotype H viruses were designated as genotype H2 [14]. A list of the measles genotypes with the year last detected, the designated reference strain(s), and GenBank accession number are provided in Table 7.

The convention for naming measles sequences representative of wild-type measles viruses has remained unchanged since 1998. The source of the RNA used to sequence the strain is specified in the prefix of the strain name (also known as the WHO name). Viral RNA isolated from virus lysates prepared from propagation of virus in cell culture (isolates) is given the prefix MVi and RNA extracted directly from clinical material has the prefix MVs. The city (or state/province) and the country, indicated by the 3-letter ISO code where the case occurred and the week and the year when onset of rash occurred, follow the prefix. Acceptable substitutes for the week (in order of preference) if rash onset is unknown are (1), the week when the specimen was collected and (2), the week that the specimen arrived at the laboratory.

Epidemiologic week. The weeks are entered as the epidemiological week (numerals 1-52) followed by a period and the year (2 digits). The epidemiologic week should be calculated from the first Monday of each week, with week 1 on or after the first Monday of the year. For example, January 1, 2012 (a Sunday) would be 52.11 and January 2, 2012 (a Monday) would be epidemiologic week 1 for 2012 (1.12). For historic samples where only the year is known, zero (0) should be used as the epidemiologic week.

If only the month and year are known, then the epidemiologic week number corresponding to the second full week in that month is used. Additional strains of the same genotype that are reported in the same epidemiologic week with the same prefix and location are distinguished by adding a slash and numeral following the 2-digit year.

The genotype determined for the measles virus can be placed in square brackets after the genotype designation but is not required. Measles sequences derived from cases with measles inclusion-body encephalitis or subacute sclerosing panencephalitis are denoted by adding (MIBE) and (SSPE), respectively, to the WHO name. Examples of the format for measles strain names are given below:
MVi/London.GBR/3.12/2 [D4]
MVs/NewYork.USA/17.11 [G3] (SSPE)

Measles strains within a genotype that meet criteria for epidemiologic relevance are designated as named strains (see section 7.2.1). The named strains provide a frame of reference for describing circulating viruses that are generally given this designation due to repeated identification of the strain in outbreaks of measles in several locations (i.e., epidemiologically significant). The named strain designation was introduced in the WER update in 2015 [19]. The nomenclature for named strains does not differ from standard genotype nomenclature.