Rubella virus
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Rubella Microchapters |
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Rubella virus On the Web |
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American Roentgen Ray Society Images of Rubella virus |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
Overview
Rubella virus is a single stranded, positive sense RNA virus (ssRNA). It is the only member of the genus Rubivirus and belongs to the family of Togaviridae. Rubella virus is only known to infect humans, and it is responsible for causing the common childhood Rubella infection. Rubella infection is also known as German Measles or Three Day Measles. The most devastating consequence is when Rubella virus infects pregnant women during their first trimester, as it may result in congenital rubella syndrome in the newborn. Rubella infection has largely been eradicated in the developed world since the introduction of the MMR vaccine. However, it is still a challenge in many parts of the developing world due to cost and availability of the MMR vaccine.
Genome Structure
The Rubella virus genome is composed of 9762 nucleotides and encodes 2 nonstructural polypeptides (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third. Both envelope proteins E1 and E2 are glycosylated. The Rubella virus has the highest concentration of G/C nucleotides of any RNA virus, with 69.5% of the genome consisting of those nucleotides. Rubella has been sequenced completely for three strains showing >95% homology between the three strains.
There are three sites that are highly conserved in Togaviruses:
- A stem-and-loop structure at the 5' end of the genome
- A 51-nucleotide conserved sequence near the 5' end of the genome and
- A 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequences are present in the rubella genome.
The genome encodes several non-coding RNA structures. Among those is the rubella virus 3' cis-acting element, which contains multiple stem-loops and one of the stem-loop structures has been found to be essential for viral replication.
Cell Structure and Life Cycle
Rubella virus is an enveloped virus, circular or oval in shape and 60nm in diameter. The virion is composed of a capsid core containing a single copy of genomic RNA. The outer membrane is a lipid bilayer containing specialized glycoproteins (E1 and E2) believed to be responsible for attachment to host cells. It is also believed that a pH of 6.0 or less induces conformational changes in the glycoproteins making attachment of the viral envelope to host cells more likely. Rubella virus likely enters cells via endocytosis. Once in the cell a conformational change occurs in the capsid shell releasing the genetic information into the cell. Replication is slow with a latency period of 8-12 hours, with structural proteins appearing at 12-16 hours and peak viral 36-48 hours after infection. In volunteer subjects infected via aerosol, the characteristic rash typically appears 16-20 days from the time of exposure.
Epidemiology
On the basis of differences in the sequence of the E1 protein, two genotypes have been described which differ by 8-10%. These have been subdivided into 13 recognised genotypes: 1a, 1B, 1C, 1D, 1E, 1F, 1G, 1h, 1i, 1j, 2A, 2B and 2C.
For typing, the WHO recommends a minimum window that includes nucleotides 8731 to 9469.
- Genotypes 1a, 1E, 1F, 2A and 2B have been isolated in China.
- Genotype 1j has only been isolated from Japan and the Philippines.
- Genotype 1E is found in Africa, the Americas, Asia and Europe.
- Genotype 1G has been isolated in Belarus, Cote d'Ivoire and Uganda.
- Genotype 1C is endemic only in Central and South America.
- Genotype 2B has been isolated in South Africa.
- Genotype 2C has been isolated in Russia.
Pathogenesis
Rubella virus only infects humans and is spread from person to person through contact or from a cough or sneeze, as the virus lives in the mucus of an infected person. The virus can be transmitted up to a week before the rash appears and one to two weeks after. Rubella is also transmitted from an infected mother to her unborn child causing congenital rubella syndrome.
Rubella Vaccination
The rubella vaccine is included as a part of the common childhood vaccination known as MMR (Measles, Mumps, Rubella) vaccination. The Meruvax II or Rubella vaccination effectively prevents the disease after a single injection in humans 12 moths or older. While antibodies are usually developed after a single infection of the virus the vaccine is vital to prevent infection of expecting mothers who could pass on the virus to their unborn fetus. The vaccine is a freeze dried sample of the Wistar RA 27/3 strain of Rubella virus which when injected induces an immunity by causing a modified rubella infection. Rubella hemagglutinin antibodies are produced to prevent infection of wild rubella virus. Vaccination with MMR is a requirement in most states for children wishing to enter school. It is not yet clearly known if the immunity is permanent, however, it is known to last for at least 10 years.