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Chapter: Microbiology and Immunology: Virology, Virus: Miscellaneous Viruses

Rubella Virus

Rubella virus causes rubella, a mild viral disease affecting the skin, lymph nodes, and less commonly, the joint. It also causes congenital rubella syndrome. It is an RNA virus classified as a rubivirus in the family Togaviridae.

Rubella Virus

Rubella virus causes rubella, a mild viral disease affecting the skin, lymph nodes, and less commonly, the joint. It also causes congenital rubella syndrome. It is an RNA virus classified as a rubivirus in the family Togaviridae.

Properties of the Virus


Rubella virus shows following features:

·           It is a pleomorphic, roughly spherical virus measuring 50–70 nm in diameter.

·           It consists of a single-stranded RNA genome, an icosahedral nucleocapsid, and lipoprotein envelope.

·            The virus unlike measles and mumps viruses has a positive-strand RNA, therefore does not contain any virion polymerase.

·           The envelope contains hemagglutinin peplomers.

 Viral replication

Rubella virus penetrates the cell and uncoats, and the positive-strand RNA genome is translated into several structural and nonstructural proteins. RNA-dependent RNA polymerase is an important nonstructural protein, which replicates the genome first by making progeny. The virion acquires its envelope from the outer membrane of cell as the virion comes out of the cell. Both replication and assembly of the virion occur in the cyto-plasm of the cell.

 Antigenic and genomic properties

Rubella has only one serotype.

 Other properties

The virus agglutinates erythrocytes of human, chick, goose, and pigeon at 4°C. The virus is heat sensitive. It is readily inactivated by heating at 56°C, but survives for several years at 260°C. The virus is inactivated by chemicals, such as beta-propiolactone, formaldehyde, chloroform, and ether.

Virus Isolation

The virus is grown with difficulty in the cell lines. The virus is not cytolytic but produces limited cytopathologic effects in certain cell lines, such as Vero and RK-13 cell lines. In cell line, the replication of rubella prevents the replication of superinfec-tious picornavirus. This phenomenon is known as heterologousinterference, which is made use of in detection of rubella virus.

Pathogenesis and Immunity

 Pathogenesis of rubella

Initially rubella virus infects the nasopharynx of the upper respiratory tract and then spreads to local lymph nodes. From there, the virus spreads by the blood throughout the body to the internal organs and skin. The occurrence of mild rash is characteristic. The exact cause of pathogenesis of rash is not known, but may be due to antigen–antibody mediated vasculi-tis. During prodromal period and for nearly 2 weeks after the onset of rash, the infected persons continue to secrete virus in the respiratory droplets.

 Host immunity

Rubella infection is characterized by development of circulat-ing antibodies, which are produced after the phase of viremia and their development correlates with the appearance of the rash. The circulating antibodies limit the spread of the virus in the blood. These antibodies also cross the placenta and protect the newborn from an attack of rubella.

Natural rubella infection usually confers lifelong immunity. Reinfection may occur occasionally after the natural disease or vaccination or exposure to the virus. The formation of immune complexes is suggested to contribute to the development of rash and arthralgia associated with rubella infection.

Clinical Syndromes

Rubella virus causes rubella and congenital rubella syndrome.


Incubation period varies from 14 to 21 days. Rubella is a milder and more subtle disease than measles. A three-day maculopap-ular or macular rash, which starts on the face and progresses downward to involve the extremities, is the characteristic pre-sentation in symptomatic cases. The rash typically lasts 3 days. Tender lymphadenopathy that affects all the nodes but most commonly affects suboccipital, postauricular, anterior, and posterior cervical nodes is the hallmark of rubella.

In adults, rubella produces a more severe disease with mani-festations of arthralgia and polyarthritis, and rarely thrombo-cytopenia or postinfectious encephalopathy.

 Congenital rubella syndrome

Congenital rubella syndrome is the most severe and important complication of rubella, which occurs in the fetus of pregnant women without immunity to the virus. The fetus is at major risk until fifth month of pregnancy. Maternal immunity to the virus due to prior exposure or vaccination prevents spread of the virus to the fetus. In the first trimester, 80% of the infants would be affected, and severity of the disease depends on how early the infection occurs. Cataract, mental retardation, and deafness are the most common manifestations of congenital rubella infection.

The congenital rubella results in congenital anomalies or even death of the fetus. In addition, the infants infected in utero continue to excrete rubella virus for up to 1 year. These children constitute a public health hazard because they are considered as an exposure threat to nonimmune pregnant women. The virus can be transmitted to pregnant women from children.


Humans are the natural host. The disease is prevalent worldwide. In countries where vaccination is not routinely used, epidemics of rubella occur every 6–9 years. Respiratory droplets are the source of infection. The virus is transmitted from person-to-person by inhalation of respiratory droplets. The infection is usually acquired during childhood. Patients are most contagious during the time of appearance of the rash. The viruses are excreted in the pharynx and in the respiratory droplets from 7 days before until 7 days after the rash. The infection is usually acquired during childhood. The infection can also be transmitted transplacentally from mother to fetus, resulting in congenital infection.

Laboratory Diagnosis


Throat swab in the adult and urine, cerebrospinal fluid (CSF), or throat swab in infants with congenital rubella are the fre-quently used specimens.

 Isolation of the virus

Viruses can be isolated in rabbit kidney (RK-13), rabbit cor-nea (SIRC), and Vero cells. The virus produces little cytopathic effects.


The diagnosis of rubella is usually confirmed by demonstra-tion of rubella antibodies in the serum. Demonstration of specific IgM rubella antibodies in a single acute phase serum sample is diagnostic of rubella. Diagnosis can also be made by demonstration of a fourfold or a greater rise in IgG antibody titer between acute phase and convalescent phase sera by using hemagglutination inhibition test or enzyme-linked immuno-sorbent assay (ELISA).

In pregnant women, demonstration of IgM rubella antibodies indicates recent infection. Demonstration of 1:8 or greater titer of IgG antibody in serum indicates immunity and consequent protection of the fetus. Demonstration of rubella virus in amniotic fluid collected by amniocentesis indicates a definite rubella infection in the fetus. The presence of IgM antibodies in the serum of the infant indicates recent infection because IgM does not cross the placenta from the mother as does IgG. Confirmation of diagnosis of congenital rubella syndrome in an infant after 1 year with serology alone is very difficult.


There is no antiviral therapy.


Preventive measures include vaccination and administration of immunoglobulins.


Prevention of rubella is best carried out by immunization with live attenuated vaccine. The main objective of rubella vaccina-tion program is to prevent congenital infection by decreasing the number of susceptible people, especially children. Vaccination causes a significant reduction of the likelihood of exposure of the pregnant women to the virus.

Immunoglobulins can be given to pregnant women in the first trimester of pregnancy who have been exposed to a known case of rubella and for whom termination of pregnancy is not an option. Nevertheless, cases of congenital rubella syndrome have occurred in infants born to mothers who received immu-noglobulins shortly after exposure. No adequate treatment is available for pregnant women exposed to rubella.

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