Genetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing.


Measles is one of the most contagious human diseases and is still responsible for considerable childhood morbidity and mortality. The causative agent, measles virus (MV), is an enveloped virus with a negative-sense single-stranded RNA genome and is a member of the genus Morbillivirus within the family Paramyxoviridae (1). MV genomes are relatively stable; the virus consists of a single serotype, and live-attenuated MV vaccines developed in the 1960s still confer protection against currently circulating wild-type MV strains. However, the MV genome also contains a number of variable regions that have been used to assign 8 genetic clades (A to H), which have been further subdivided into 24 genotypes (or subtypes) (2). The MV genome is typically 15,894 nucleotides (nt) in length, and it encodes 6 structural proteins (N, P, M, F, H, and L) and two nonstructural proteins (V and C).
Viral isolates of circulating wild-type MV strains provide an important resource for virology and vaccine development. In this work, we have obtained complete genome sequences for the following six wild-type MV strains: MVi/Khartoum.SUD/34.97/2 [B3], a strain endemically circulating in Khartoum (Sudan) in 1997 (3); MVi/Bilthoven.NLD/1991 [C2], a strain isolated during a measles outbreak in The Netherlands in 1991 (4); MVi/Amsterdam.NLD/19.11 [D4], an unpublished import case into The Netherlands isolated in 2011 from a patient who had traveled to Greece; MVi/Dodewaard.NLD/29.13 [D8], an isolate obtained during a large measles outbreak in The Netherlands in 2013 (5); MVi/Amsterdam.NLD/49.97 [G2], an isolate obtained from a secondary case in a hospital outbreak in 1997 (6); and MVi/Amsterdam.NLD/27.97, a virus isolated from a measles patient in 1997 with a recent history of travel to China (7). All viruses were isolated in Epstein-Barr virus-transformed human B-lymphoblastic cell lines, followed by short-term culture (maximum 3 passages) in Vero cells expressing human CD150 (8). All cultures were confirmed negative for Mycoplasma spp. All virus isolates are available via the European Virus Archive (https://www.european-virus-archive.com).
Total viral nucleic acid was extracted from 6 virus cultures (with titers between 105 and 107 50% tissue culture infective dose [TCID50]/ml), using Bioke extraction reagents (Leiden, The Netherlands). Extracted RNA was reverse transcribed and second-strand synthesis was performed using random primers as previously described (9), followed by sequencing on the Ion Torrent S5XL platform to generate 2.2 × 106 to 2.8 × 106 400-nt reads per sample. Raw reads were trimmed from the 3′ end to a median Phred score of 30 and minimum length of 75 nt using the Quality Assessment of Short Read (QUASR) package (10), and then de novo assembled using SPAdes version 3.11 (11).
Six complete MV genomes were obtained, including the first full genome for MV genotype C2. Of note, one MV genome (MVi/Amsterdam.NLD/19.11 [D4]) had a 6-nucleotide insertion, giving rise to a full genome length of 15,900 nt and complying with the rule of six for replication competency in MV (12). These sequence data will provide a useful reference for measles surveillance and for studies to better understand MV evolution and biology.

Accession number(s).

The MV sequences described in this study have been deposited in GenBank under the accession numbers MG912589 to MG912594.


We thank Ronald van Marion and Winand Dinjens for their sequencing support.
This work was funded by the EU Horizon 2020 programs EVAg (grant 653316), COMPARE (grant 643476), and Virogenesis (grant 634650).


Rota PA, Moss WJ, Takeda M, De Swart RL, Thompson KM, Goodson JL. 2016. Measles. Nat Rev Dis Primers 2:16049.
World Health Organization 2015. Genetic diversity of wildtype measles viruses and the global measles nucleotide surveillance database (MeaNS). Wkly Epidemiol Rec 30:373–380.
El Mubarak HS, van de Bildt MWG, Mustafa OA, Vos HW, Mukhtar MM, Ibrahim SA, Andeweg AC, El Hassan AM, Osterhaus ADME, de Swart RL. 2002. Genetic characterization of wild-type measles viruses circulating in suburban Khartoum, 1997–2000. J Gen Virol 83:1437–1443.
van Binnendijk RS, van der Heijden RWJ, van Amerongen G, UytdeHaag FGCM, Osterhaus ADME. 1994. Viral replication and development of specific immunity in macaques after infection with different measles virus strains. J Infect Dis 170:443–448.
Woudenberg T, van Binnendijk RS, Sanders EAM, Wallinga J, de Melker HE, Ruijs WLM, Hahné SJM. 2017. Large measles epidemic in The Netherlands, May 2013 to March 2014: changing epidemiology. Euro Surveill 22.
de Swart RL, Wertheim-van Dlllen PME, van Binnendijk RS, Muller CP, Frenkel J, Osterhaus ADME. 2000. Measles in a Dutch hospital introduced by an immunocompromised infant from Indonesia infected with a new virus genotype. Lancet 355:201–202.
Truong AT, Mulders MN, Gautam DC, Ammerlaan W, de Swart RL, King CC, Osterhaus ADME, Muller CP. 2001. Genetic analysis of Asian measles virus strains—new endemic genotype in Nepal. Virus Res 76:71–78.
Ono N, Tatsuo H, Hidaka Y, Aoki T, Minagawa H, Yanagi Y. 2001. Measles viruses on throat swabs from measles patients use signaling lymphocytic activation molecule (CDw150) but not CD46 as a cellular receptor. J Virol 75:4399–4401.
Phan MVT, Anh PH, Van Cuong N, Oude Munnink BB, van der Hoek L, Tri TN, Bryant JE, Baker S, Thwaites G, Woolhouse M, Kellam P, Rabaa MA, Cotten M. 2016. Unbiased whole-genome deep sequencing of human and porcine stool samples reveals circulation of multiple groups of rotaviruses and a putative zoonotic infection. Virus Evol 2:58875.
Watson SJ, Welkers MRA, Depledge DP, Coulter E, Breuer JM, de Jong MD, Kellam P. 2013. Viral population analysis and minority-variant detection using short read next-generation sequencing. Philos Trans R Soc Lond B Biol Sci 368:20120205.
Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, Lesin VM, Nikolenko SI, Pham S, Prjibelski AD, Pyshkin AV, Sirotkin AV, Vyahhi N, Tesler G, Alekseyev MA, Pevzner PA. 2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19:455–477.
Bankamp B, Liu C, Rivailler P, Bera J, Shrivastava S, Kirkness EF, Bellini WJ, Rota PA. 2014. Wild-type measles viruses with non-standard genome lengths. PLoS One 9:e95470.

Information & Contributors


Published In

cover image Genome Announcements
Genome Announcements
Volume 6Number 1329 March 2018
eLocator: 10.1128/genomea.00184-18


Received: 12 February 2018
Accepted: 27 February 2018
Published online: 29 March 2018



Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
Claudia M. E. Schapendonk
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
Bas B. Oude Munnink
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
Marion P. G. Koopmans
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands
Matthew Cotten
Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands


Address correspondence to Matthew Cotten, [email protected].

Metrics & Citations



  • For recently published articles, the TOTAL download count will appear as zero until a new month starts.
  • There is a 3- to 4-day delay in article usage, so article usage will not appear immediately after publication.
  • Citation counts come from the Crossref Cited by service.


If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.

View Options

Figures and Media






Share the article link

Share with email

Email a colleague

Share on social media

American Society for Microbiology ("ASM") is committed to maintaining your confidence and trust with respect to the information we collect from you on websites owned and operated by ASM ("ASM Web Sites") and other sources. This Privacy Policy sets forth the information we collect about you, how we use this information and the choices you have about how we use such information.
FIND OUT MORE about the privacy policy