Genetic Analysis of Mumps Viruses

Key points

  • Genetic information from circulating mumps viruses is used to track transmission pathways and suggest epidemiological links between cases and outbreaks.
  • VPD-Reference Centers and CDC perform genotyping, based on the sequence of the gene coding for the small hydrophobic protein.
  • Send patient specimens from positive sporadic cases of mumps as well as representative specimens from an outbreak.
Thin sectioned transmission electron micrograph (TEM) depicting cell cultured mumps virions

About mumps genotypes

Mumps strains are assigned to 1 of 12 genotypes (genetic constitutions) based on the sequences of the gene coding for the short hydrophobic (SH) protein. In some circumstances, a genotype has been associated with endemic circulation of mumps virus in a country; however, routine genotype surveillance for mumps is limited to only a few countries.

Mumps outbreaks are typically associated with only one genotype. The genetic information from circulating mumps viruses is used to:

  • Track the transmission pathways of the virus.
  • Suggest epidemiologic links, or lack thereof, between cases and outbreaks.

Genetic characterization of mumps viruses

Since CDC initiated routine genotype surveillance for mumps in 2006, CDC and APHL-VPD Reference Centers have detected mostly genotype G among people with mumps in the United States. A few of the other 11 genotypes were also detected, but they are usually associated with mumps importations into the United States and have not been associated with large outbreaks. No differences are present in the genotypes detected in vaccinated and unvaccinated U.S. mumps patients.

See Also: Genetic characterization of mumps viruses associated with the resurgence of mumps in the United States: 2015–2017

Collecting & submitting specimens

Specimens for genotyping can be sent to the CDC or APHL-VPD Reference Centers.

Laboratory Testing for Mumps
Find information about the lab tests used to identify mumps and specimen collection best practices.
Mumps Specimen Collection
Learn how to clinically collect and submit specimens for mumps testing.
Mumps Clinical Testing
Use this visual tool when communicating mumps testing procedures to providers.

rRT-PCR results

A positive rRT-PCR signal indicates the presence of mumps virus RNA in the patient sample.

Failure to detect mumps virus RNA by rRT-PCR in specimen from a person with clinically compatible mumps symptoms does not rule out mumps as a diagnosis.

Keep Reading: Virus Detection & What Test Results Mean

Genotyping in public health investigations

Laboratories are encouraged to send patient specimens from positive sporadic cases of mumps as well as representative specimens from an outbreak. The sequence of the mumps small hydrophobic (SH) gene is used to assign mumps viruses to 1 of 12 recognized genotypes. The sequence information may help to identify the source of the virus and can provide confirmation of suspected epidemiologic links.

Obtaining specimens for outbreaks

During ongoing outbreaks, it is not necessary to obtain a genotype on every rRT-PCR positive specimen, although it is recommended to obtain representative sequences on a weekly basis. However, if the outbreak spreads to another community, an effort should be made to obtain a genotype for specimens from the new outbreak. Specimens should also be submitted for genotyping from confirmed cases that do not meet the case definition, if they have an unusually long incubation period or a travel history (domestic or international).

Keep Reading: Strategies for the Control and Investigation of Mumps Outbreaks

RT-PCR & real-time PCR protocols

The following RT-PCR and real-time RT-PCR protocols for mumps testing are available online:

Obtaining control materials

CDC can provide a sample of synthetic RNA for real-time RT-PCR reactions (N gene) and for genotyping (endpoint) RT-PCR (SH gene). This material is ready to use in RT-PCR reactions.

If laboratories want to produce their own RNA specimen or require a positive control for virus isolation, viruses can be obtained from ATCC or BEI. A proficiency test for mumps RT-PCR can be obtained from the Wisconsin State Laboratory of Hygiene.

Contact information ‎

Public health laboratories, or laboratories affiliated with state public health laboratories, may send requests for mumps RNA to Dr. Paul Rota.
Email

Considerations for genetic changes

Effects on molecular diagnostics:

Viruses like mumps have very high rates of genetic change compared to other organisms. The CDC diagnostic assay, rRT-PCR, is designed to detect a specific sequence that is conserved in many mumps genotypes. If genetic changes occur in the sequence detected by rRT-PCR, the assay may lose the ability to detect mumps virus with high sensitivity.

CDC monitors the RT-PCR assay performance in collaboration with the four APHL-VPD Reference Centers. State laboratories performing the rRT-PCR assay to detect mumps may participate in a proficiency testing program that was developed by CDC and the APHL-VPD Reference Centers. The program is managed by the Wisconsin State Laboratory of Hygiene.

Effects on vaccines:

Not all genetic changes result in a change in viral proteins. "Silent mutations" change the genetic sequence without changing the predicted protein.

Viral proteins are recognized by the host's immune system. There are several viral proteins, each containing many recognition sites. Therefore, it would take many genetic changes to change the viral proteins to the extent that they are no longer recognized by the immune response in vaccinated individuals. CDC is developing tests to monitor the ability of serum from vaccinated individuals to neutralize currently circulating strains.

Resources

Print
Content Source:
National Center for Immunization and Respiratory Diseases; Division of Viral Diseases
  • Bitsko RH, Cortese MM, Dayan GH, Rota PA, Lowe L, Iversen SC, Bellini WJ. Detection of RNA of mumps virus during an outbreak in a population with a high level of measles, mumps, and rubella vaccine coverage. J Clin Microbiol 2008;46:1101–3.
  • Briss PA, Fehrs LJ, Parker RA, Wright PF, Sannella EC, Hutcheson RH, Schaffner W. Sustained transmission of mumps in a highly vaccinated population: assessment of primary vaccine failure and waning vaccine-induced immunity. J Infect Dis 1994;169:77–82.
  • Davidkin I, Jokinen S, Paananen A, Leinikki P, Peltola H. Etiology of mumps-like illnesses in children and adolescents vaccinated for measles, mumps, and rubella. J Infect Dis 2005;191:719–23.
  • Gouma S, Vermeire T, Van Gucht S, et al. Differences in antigenic sites and other functional regions between genotype A and G mumps virus surface proteins. Sci Rep. 2018;8(1):13337.
  • Gut JP, Lablache C, Behr S, Kirn A. Symptomatic mumps virus reinfections. J Med Virol 1995;45:17–23.
  • Hatchette TF, Mahony JB, Chong S, LeBlanc JJ. Difficulty with mumps diagnosis: what is the contribution of mumps mimickers? J Clin Virol 2009; 46:381-3.
  • Jin, L., et al., Genomic diversity of mumps virus and global distribution of the 12 genotypes. Rev Med Virol, 2015. 25(2): p. 85-101.
  • Jin L, Feng Y, Parry R, Cui A, Lu Y. Real-time PCR and its application to mumps rapid diagnosis. J Med Virol 2007; 79:1761-7.
  • Krause CH, Eastick K, Ogilvie MM. Real-time PCR for mumps diagnosis on clinical specimens–comparison with results of conventional methods of virus detection and nested PCR. J Clin Virol 2006; 37:184-9.
  • Krause CH., Molyneaux PJ, Ho-Yen DO, McIntyre P, Carman WF, Templeton KE. Comparison of mumps-IgM ELISAs in acute infection. J Clin Virol 2007;38:153–6.
  • L'Huillier AG, Eshaghi A, Racey CS, et al. Laboratory testing and phylogenetic analysis during a mumps outbreak in Ontario, Canada. Virol J 2018; 15:98.
  • Maillet M, Bouvat E, Robert N, et al. Mumps outbreak and laboratory diagnosis. J Clin Virol 2015; 62:14-9.
  • Narita M, Matsuzono Y, Takekoshi Y, Yamada S, Itakura O, Kubota M, Kikuta H, Togashi T. Analysis of mumps vaccine failure by means of avidity testing for mumps virus-specific immunoglobulin G. Clin Diagn Lab Immunol 1998;5:799–803.
  • Nunn A, Masud S, Krajden M, Naus M, Jassem AN. Diagnostic Yield of Laboratory Methods and Value of Viral Genotyping during an Outbreak of Mumps in a Partially Vaccinated Population in British Columbia, Canada. J Clin Microbiol. 2018;56(5).
  • Rota JS, Rose JB, Doll MK, McNall RJ, McGrew M, Williams N, Lopareva EN, Barskey AE, Punsalang Jr A, Rota PA, Oleszko WR, Hickman CJ, Zimmerman DM, Bellini WJ. Comparison of the sensitivity of laboratory diagnostic methods from a well-characterized outbreak of mumps in New York City in 2009. Clin Vaccine Immunol. 2013;20:391-6.
  • Rota JS, Turner JC, Yost-Daljev MK, Freeman M, Toney DM, Meisel E, Williams N, Sowers SB, Lowe L, Rota PA, Nicolai LA, Peake L, Bellini WJ. Investigation of a mumps outbreak among university students with two measles-mumps-rubella (MMR) vaccinations, Virginia, September–December 2006. J Med Virol 2009;81:1819–25.
  • Rubin SA, Qi L, Audet SA, et al. Antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralizes a heterologous wild-type mumps virus associated with a large outbreak. J Infect Dis. 2008;198(4):508-515.
  • Sakata H, Tsurudome M, Hishiyama M, Ito Y, Sugiura A. Enzyme-linked immunosorbent assay for mumps IgM antibody: comparison of IgM capture and indirect IgM assay. J Virol Methods 1985;12:303–11.
  • Sartorius B, Penttinen P, Nilsson J, Johansen K, Jönsson K, Arneborn M, Löfdahl M, Giesecke J. An outbreak of mumps in Sweden, February–April 2004. Euro Surveill 2005;10 (9):pii=559. Available at https://www.eurosurveillance.org/content/10.2807/esm.10.09.00559-enexternal icon
  • Tan KE, Anderson M, Krajden M, Petric M, Mak A, Naus M. Mumps virus detection during an outbreak in a highly unvaccinated population in British Columbia. Can J Public Health 2011; 102:47-50.
  • Vermeire T, Barbezange C, Francart A, et al. Sera from different age cohorts in Belgium show limited cross-neutralization between the mumps vaccine and outbreak strains. Clin Microbiol Infect. 2018.