The fate of the infected cell is determined by the replicative strategy of the virus and this in turn can be predicted from the structure of the virus particle and its genomic organisation. Viral taxonomy can be used to predict the biological behaviour and hence the pathogenic potential and course of infection at the level of the individual patient and the community.
Rubella is a medium sized (60nm) enveloped virus with an unsegmented positive strand RNA genome.
The core has helical symmetry. Its nearest relatives are the Togaviruses, which are a group of arboviruses. The rubella genome of approximately 12Kb codes for the 3 structural proteins which are part of the infectious particle or virion and a number of non-structural proteins, which include a RNA polymerase. The viral envelope consists of cell membrane modified by the insertion of viral encoded glycopeptides. Compare rubella with herpes simplex, a DNA virus which is also enveloped and with polio, a naked RNA virus.
Rubella multiplies relatively slowly in cell cultures, a single cycle occupying 48-72 hours compared with only 6 hours for polio.
The classic stages comprising absorption, penetration, eclipse, viral assembly and release occur without causing immediate cell death. The interaction of rubella with its host cell is more subtle and passage reveals that the cell growth is very considerably slowed.
The mechanism of this growth retardation has not been elucidated. Another virus which causes striking arrest of cell growth is the parvovirus B19, but other viruses e.g. herpes and retroviruses are often associated with accelerated cell growth and malignant transformation. Although rubella grows reasonably well in laboratory cell cultures, it does not produce obvious cell damage so its presence was initially difficult to demonstrate. Advantage was taken of the production of interferon by infected cells so that cultures where rubella was growing resisted superinfection with another virus (Coxsackie B) that was inhibited by the cytokine.
Once virus was grown and purified in vitro, it became easy to stain infected cells with fluorescent-labelled antibody. More recently still, molecular techniques such as RT PCR have been used to examine cultures and tissues for evidence of rubella virus. Although infected cells are not killed by rubella, their ability to divide is significantly impaired. This is the basis of their effect on the developing fetus, whereas the symptoms of acute rubella in children and adults is due to generation of immune complexes of virus and antibody.
A specific interaction between viral genes and cell regulatory elements is often observed: parvovirus B19 will only replicate in actively dividing cells, herpes virus and retroviruses often stimulate cell division and may cause malignant transformation, papillomaviruses replicate only in terminally differentiated keratinocytes. Cultured virus was also found to agglutinate human and avian erythrocytes through the interaction with the viral receptor with cell surface receptors.
This was used to develop specific antibody tests because the critical antibody conferring immunity interacts with the viral receptor and inhibits this reaction. This haemagglutination inhibition test has now been superceded by technically simpler ELISA assays but it remains an important technique for studying virus/cell interactions for many enveloped viruses including influenza, measles and many arboviruses. Recovery from rubella and subsequent immunity are mediated by different arms of the immune system.
While some viruses effectively kill all infected cells, others result in cell death by apoptosis and still others are removed by specific activated lymphocytes. Rubella spreads by the respiratory route and is relatively fragile in the environment. Transmission is relatively less efficient than measles or influenza and this accounts for its characteristic epidemiological pattern.
Mathematical models incorporating this parameter are important tools in predicting the course of outbreaks and the effect of control strategies. The active component of rubella vaccine is live attenuated virus. Inactivated vaccines have been unsatisfactory. Both the technical problems of production and the pathogenesis of disease determine the choice between inactivated and attenuated vaccines. Current rubella vaccines are made in primate cell cultures.
- Provides an excellent overview of virus structure and replication
Mims, C., 2008, Medical microbiology, 4th. edn., Mosby, London: Philadelphia. Chapter 12.
- Is a good introduction to interferon and the systemic effects of virus infection. A general account of cell receptors, including viral ones, can be found in Fenner, White. Chapter 7.