Introduction

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Image from White and Fenner. Medical Virology: Fourth edition, 1994.

The Togavirus family falls into the category of group A arboviruses, viruses which are transmitted by blood-sucking insects. The virion is composed of ss positive stranded RNA which is 10-12 kilobases long and is 70 nm in diameter. Because the viral RNA is plus stranded, capped at its 5' end and poly-adenylated at its 3' end, it can function as mRNA. The genome is enclosed within an icosahedral capsid. A surrounding envelope composed of two glycoproteins, E1 and E2 is tightly bound to the capsid. These proteins serve as neutralizing epitopes as well as means for distinguishing between species. It has also been speculated that the E2 protein may have a direct role in the binding of virus to host cells, acting as a tropogen, which attaches itself to the viral receptor on the host cell. Studies have shown that neutralizing the E2 protein with antibodies impairs the virus' ability to infect a cell. Replication takes place within the cytoplasm as is the norm for all RNA viruses (with the exception of retroviruses).

The togaviridae family is divided into two genera, the alphaviruses and the rubiviruses. The only member of the rubivirus genus is the rubella viurs (also known as German measles). The alphavirus genus is comprised of 27 arboviruses which are primarily transmitted through mosquitos or ticks. Rubella on the other hand is primarily transmitted either through direct contact, inhalation of aerosol containing virus, or congenitally from mother to child.

Infection with alphaviruses can lead to symptoms ranging from fever and rash to lethal encephalitis or persistent arthritis. Rubella infection normally leads to a mild rash and a fever that is usually inconspicuous. It is therefore classified as the 3rd disease within Filatov's six red rashes of childhood. The more common manifestation of rubella is that of congenital transmission leading to a disorder known as congenital rubella syndrome. 20% of infants that are infected within the first trimester develop severe abnormalities. These include deafness, blindness, especially due to cataracts, congenital heart disease, particularly patent ductus arteriosus, microcephaly with mental retardation, bone translucency, and retardation of growth. Along with these defects, nearly 20% of children with CRS may develop insulin-dependent diabetes mellitus as adolescents.

Of the alphaviruses, three are major causes of encephalitis: Western Equine encephalitis, Eastern Equine encephalitis, and Venezuelan Equine encephalitis. Typical symptoms of these infections include fever, followed by drowsiness and neck stiffness, and may develop into confusion, paralysis, convulsions, and possible coma. Survivors are normally left with sequale such as mental retardation and paralysis.

Western Equine encephalitis was first isolated in the U.S in 1930. It is typically seen in the western plain states due to outbreaks in horses. Most cases are inapparent although mortality rates can reach 3%-4%. Individuals over 55 show higher mortality. Virus is spread by the mosquito Culex tarsalis which breeds in ditches. Since the virus can multiply at cool temperatures, epidemics normally occur early in summer and may also be seen farther north into Canada.

Eastern Equine encephalitis is rare yet deadly. The virus was first isolated in the U.S in 1933 and is transmitted by Culiseta melanura. The mosquito resides in fresh water swamps and rarely bites mammals, hence the rare appearance of this disease in humans. However, in the event that infection does occur, and it leads to encephalitis, the mortality rate may reach as high as 90%. Children appear to be more susceptible to infection and show more abrupt onset of symptoms. A vaccine is currently available for lab workers and for horses.

Venezuelan Equine encephalitis virus is maintained in the forests and marshes of tropical America. For the most part the virus circulates around rodents via the mosquito Culex melanoconion. VEE does not pose a significant problem in the U.S. as most humans who become infected usually only suffer from fever an myalgia and encephalitis is not normally seen. There is a vaccine available for horses. A related virus known as the VEE II Everglades virus has been documented in central nervous system cases reported in Florida. It is very infectious through inhalation of virus-containing aerosol and is highly prevelant in Florida.

Another set of alphaviruses are responsible for causing fevers, rashes and forms of arthritis. Among these are the Chikungunya virus, the O'nyong-nyong virus, the Mayaro virus, the Ross River virus and the Sinbis virus. Infection with these viruses tends to produce a similar set of symtoms following an incubation period of approximately 2-3 days:abrupt onset of fever, chills, myalgia and sever polyarthralgia and a maculopapular rash will then typically appear. Other common alphavirus is the Semliki Forest virus which has proven to be very effective in research aimed at understanding features such as viral translation and features of membrane glycoproteins.


CryoEm image of Semliki Forest virus from Garry Lab website (Big Picutre Book of Viruses)