Rubella Virus


Rubella virus is a human virus belonging to the family Togaviridae and the sole member of the rubivirus genus. Rubella virus has a small genome composed of single‐stranded RNA and produces only five proteins. The rubella virus replication cycle takes place entirely within the cytoplasm of the infected cell. Rubella virus establishes a body‐wide or systemic infection that is manifested by mild symptoms including rash, lymph node swelling and low‐grade fever. However, rubella virus is an important human pathogen because it causes a spectrum of serious birth defects known collectively as congenital rubella syndrome (CRS) when a mother lacking immunity is infected during the first trimester of pregnancy. CRS can include blindness, deafness, mental retardation, heart malformations and endocrine dysfunctions. Before development of effective live, attenuated vaccines, rubella virus was the leading teratogenic agent of an infectious nature. Through use of these vaccines, rubella and CRS are controlled in much, but not all, of the world and are targeted for elimination in the Western Hemisphere and Europe.

Key Concepts:

  • Rubella virus causes a benign systemic illness characterised by a rash, but is a dangerous teratogen when infection occurs during pregnancy.

  • Fetal infection by rubella virus results in congenital rubella syndrome, a constellation of serious birth defects, particularly deafness, blindness and mental retardation.

  • Rubella virus is classified in the Togaviridae family and is the only member of the rubivirus genus.

  • Rubella virions are pleiomorphic, approximately 70 nm in diameter and consist of a quasispherical capsid containing the genome RNA surrounded by an envelope composed of a lipid bilayer from which protrude glycoprotein spikes.

  • The rubella virus genome is a plus‐polarity RNA, 10 000 nucleotides in length, which encodes only five proteins: P150 and P90, both of which participate in RNA replication in the infected cells, and capsid (C) and envelope glycoproteins 1 and 2 (E1 and E2) which comprise the virion.

  • In the infected cell, rubella virus replication takes place entirely within the cytoplasm.

  • In the infected cell, rubella virus RNA replication, which proceeds through an RNA intermediate, takes place in association with cell membranes.

  • In the infected cell, rubella virion formation takes place in association with the Golgi apparatus and virions are released by exocytosis.

  • Rubella virus isolates worldwide cluster into 13 genotypes that fit into two distinct clades with an overall diversity at the nucleotide level of approximately 10%, a very low level for an RNA virus.

  • Live, attenuated rubella virus vaccines, available since approximately 1970, have been used successfully to control or eliminate rubella in developed countries whereas implementation of these vaccines is progressing, but not complete, in undeveloped countries of the world.

Keywords: German measles; birth defects; pregnancy; measles

Figure 1.

Cryo‐electron micrograph of rubella virions.

Figure 2.

Rubella virus genome. The organisation of the rubella virus genome is illustrated; (UTRs) are shown as solid lines and (ORFs) as boxes. The primary translation product of each ORF is a precursor that is proteolytically processed to produce the mature proteins shown below the ORF. Within the nonstructural protein ORF, the letters denote domains predicted to have the following activities: capping (methyl transferase, MT), Q domain (Q), ADP‐ribose‐1″‐monophosphatase (X), protease (P), helicase (H) and RNA‐dependent RNA polymerase (replicase, R).

Figure 3.

Replication strategy of rubella virus. This diagram shows the translation of the nonstructural protein open reading frame (ORF) from the genome RNA, the synthesis of a genome‐length minus‐strand RNA from the genome RNA template, the use of the minus‐strand RNA as a template for the synthesis of both the genome and subgenomic RNA, and the translation of the structural protein ORF from the subgenomic RNA.

Figure 4.

Construction of rubella virus infectious clone and its use in generating virus.

Figure 5.

Congenital cataract, one of the most readily recognised symptoms indicative of congenital rubella syndrome.



Adamo MP, Zapata M and Frey TK (2008) Analysis of gene expression in fetal and adult cells infected with rubella virus. Virology 370: 1–11.

Beatch MD, Everitt JC, Law LJ and Hobman TC (2005) Interactions between rubella virus capsid and host protein p32 are important for virus replication. Journal of Virology 79: 10807–10820.

Bedford HE and Elliman DA (2010) MMR vaccine and autism. British Medical Journal 340: c655.

Centers for Disease Control and Prevention (2008) Recommendations from an ad hoc Meeting of the WHO Measles and Rubella Laboratory Network (LabNet) on use of alternative diagnostic samples for measles and rubella surveillance. Morbidity and Mortality Weekly Report 57(24): 657–660.

Centers for Disease Control and Prevention (2010) Progress toward control of rubella and prevention of congenital rubella syndrome – worldwide, 2009. Morbidity and Mortality Weekly Report 59: 1307–1310.

Fontana J, López‐Iglesias C, Tzeng WP et al. (2010) Three‐dimensional structure of rubella virus factories. Virology 405: 579–591.

Frey TK, Abernathy ES and Bosma TJ (1998) Molecular analysis of rubella virus epidemiology across three continents, North America, Europe, and Asia, 1961–1997. Journal of Infectious Diseases 178: 642–650.

Hensley E and Briars L (2010) Closer look at autism and the measles–mumps–rubella vaccine. Journal of the American Pharmacy Association 50: 736–741.

Ilkow CS, Mancinelli V, Beatch MD and Hobman TC (2008) Rubella virus capsid protein interacts with poly(a)‐binding protein and inhibits translation. Journal of Virology 82: 4284–4294.

Ilkow CS, Weckbecker D, Cho WJ et al. (2010) The rubella virus capsid protein inhibits mitochondrial import. Journal of Virology 84: 119–130.

Law LJ, Ilkow CS, Tzeng WP et al. (2006) Analyses of phosphorylation events in the rubella virus capsid protein: role in early replication events. Journal of Virology 80: 6917–6925.

Liang Y and Gillam S (2001) Rubella virus RNA replication is cis‐preferential and synthesis of negative‐ and positive‐strand RNAs is regulated by the processing of nonstructural protein. Virology 282: 307–319.

Matthews JD, Tzeng WP and Frey TK (2009) Determinants of subcellular localization of the rubella virus nonstructural replicase proteins. Virology 390: 315–323.

Matthews JD, Tzeng WP and Frey TK (2010) Analysis of the function of cytoplasmic fibers formed by the rubella virus nonstructural replicase proteins. Virology 406: 212–227.

Poland GA and Spier R (2010) Fear, misinformation, and innumerates: how the Wakefield paper, the press, and advocacy groups damaged the public health. Vaccine 28: 2361–2362.

Pugachev KV, Abernathy ES and Frey TK (1997) Improvement of the specific infectivity of the rubella virus (RUB) infectious clone: determinants of cytopathogenicity induced by RUB map to the nonstructural proteins. Journal of Virology 71(1): 562–568.

Pugachev KV, Tzeng WP and Frey TK (2000) Development of a rubella virus vaccine expression vector: use of a picornavirus internal ribosome entry site increases stability of expression. Journal of Virology 74: 10811–10815.

Sakata M and Nakayama T (2010) Protease and helicase domains are related to the temperature sensitivity of wild‐type rubella viruses. Vaccine [4 December, Epub ahead of print].

Reef SE and Cochi SL (2006) The evidence for the elimination of rubella and congenital rubella syndrome in the United States: a public health achievement. Clinical Infectious Diseases 43(suppl. 3): S123–S125.

Tzeng WP and Frey TK (2002) Mapping the rubella virus subgenomic promoter. Journal of Virology 76: 3189–3201.

Tzeng WP and Frey TK (2005) Rubella virus capsid protein modulation of viral genomic and subgenomic RNA synthesis. Virology 337: 327–334.

Tzeng WP and Frey TK (2009) Functional replacement of a domain in the rubella virus p150 replicase protein by the virus capsid protein. Journal of Virology 83: 3549–3555.

World Health Organization (2007) Update of standard nomenclature for wild‐type rubella viruses. Weekly Epidemiological Record 82: 216–222.

Zhou Y, Tzeng WP, Yang W et al. (2007a) Identification of a Ca2+ binding domain in the rubella virus non‐structural protease. Journal of Virology 81: 7517–7528.

Zhou Y, Tzeng WP, Ye Y et al. (2009) A cysteine‐rich metal‐binding domain from rubella virus non‐structural protein is essential for viral protease activity and virus replication. Biochemical Journal 417: 477–483.

Zhou Y, Ushijima H and Frey TK (2007b) Genomic analysis of diverse rubella virus genotypes. Journal of General Virology 88: 932–941.

Further Reading

Banatvala JE and Brown DW (2004) Rubella. Lancet 363: 1127–1137.

Frey TK (1994) Molecular biology of rubella virus. Advances in Virus Research 44: 69–160.

Frey TK (1997) Neurological aspects of rubella virus infection. Intervirology 40: 167–175.

Hobman TC and Chantler JK (2007) Rubella virus. In: Knipe DM and Howley PM (eds) Fields Virology, 5th edn, pp. 1069–1100. Philadelphia: Lippincott Williams and Wilkins.

Ilkow CS, Willows SD and Hobman TC (2010) Rubella virus capsid protein: a small protein with big functions. Future Microbiology 5: 571–584.

Plotkin SA and Reef SE (2008) Rubella vaccines. In: Plotkin SA, Orenstein WA and Offit PA (eds) Vaccines, 5th edn, pp. 735–771. Philadelphia: WB Saunders.

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Frey, Teryl K, and Matthews, Jason D(Aug 2011) Rubella Virus. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000432.pub2]