History and Timeline

The togavirus family has seen quite a few changes throughout its history. For years it was placed within the same family as flaviviruses based on similarities in structure, genome characteristics (ss plus stranded RNA, non-segemented genome, approx. 11 Kb., etc), and of course the fact that they were both transmitted through an arthropod vector. However, with the advent of new sequencing techniques and technologies within molecular biology, enough differences were found between the togaviruses and flaviviruses that the latter were moved to a separate family. Among these differences were that the flaviviruses contain their structural proteins at the 5'end, as opposed to the togaviruses whose structural proteins are found at the 3' end, the flaviviruses do not produce a sub-genomic message as the togaviruses do, and the flavivirus viral genome is capped at the 5' end but not polyadenylated at the 3'end as is found in togaviruses. The flavivirus genus within the newly formed flavivirus family then fell into the category of the group B arboviruses.

Not all of the togaviruses are transmitted through arthropods however. The rubivirus genus is composed of only one virus: the rubella virus. Rubella has been known to be a distinct disease since the early 1800's. For hundreds of years rubella was seen as a common disease that just about every child would get, somewhat like chickenpox today. Children would normally develop a rash and a slight fever. In essence the disease was not perceived as being too serious. That all changed in 1941, when an ophthalmologist known as Normann Gregg discovered an astounding amount of young children with cataracts, often accompanied by a number of congenital defects. He also noticed that this rise in cataract frequency came right after a large outbreak of rubella. Further research showed that the rubella virus could be devastating to the fetus if the mother became infected during pregnancy. These effects came to be known as congenital rubella syndrome, which is characterised by deafness, blindness, heart disease and possibly mental retardation. Gregg's discovery not only shed new light on rubella itself, but also gave rise to the idea of viruses acting as teratogens, which is a hot topic in research today, pertaining to viruses such as cytomegalovirus and congenital cytomegalic inclusion disease, whose symptoms range from jaundice to mental retardation and hearing loss. The rubella vaccine, developed in 1969 and combined with the measles and mumps vaccines in 1972, has been crucial in the prevention of rubella in the U.S., along with its congenital effects.

The following are important dates in the history of the Togaviridae family:

Early 1800's-Rubella is identified as a distinct disease

1930-Western Equine Encephalitis virus is first isolated in the United States (1st alphavirus ever isolated)

1933-Eastern Equine Encephalitis virus is first isolated in the United States.

1938- Venezuelan Equine Encephalitis is isolated.

1941-Western Equine Encephalitis epidemic is seen in the United States. It affects 300,000 horses and 3,336 humans.

1941-Normann Gregg notices large number of children with cataracts following a rubella outbreak. This and other defects are then categorized under the congenital rubella syndrome.

1942-Semliki Forest virus is isolated in Buliyama, Bwamba County, Uganda.

1952-Sindbis virus is isolated in the Sindbis health district, 40 miles north of Cairo, Egypt.

1959-Ross River virus is isolated from Aedes vigilax mosquitoes which were trapped at the Ross River in Australia.

1962-Rubella virus is isolated in culture.

1963-Ross River virus, which causes epidemic polyarthritis (mostly seen in Australia), is isolated by Doherty and colleagues.

1964-The last major epidemic of Rubella in the United States is seen. Approximately 20,000 infants are left with permanent damage following in-utero rubella exposure.

1969-Rubella vaccine is licensed

1971- Last epidemic of Venezuelan equine encephalitis is seen in horses in southern Texas.

1972- The rubella vaccine is combined with the measles and mumps vaccines to form the Measles/Mumps/Rubella (MMR) vaccine.

1986- Barmah Forest virus is identified as causing human disease in Australia.

1991-92- Most recent worldwide epidemic of rubella. Probably due to vaccine failures and missed vaccinations.