MicrobiologyBytes: Virology: Togoviruses Updated: September 11, 2007 Search

Togaviruses

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Group IV: (+)sense RNA Viruses

Family

Genus

Type Species

Hosts

Togaviridae

Alphavirus

Sindbis virus

Vertebrates

Rubivirus

Rubella virus

Vertebrates

Morphology ->

Enveloped, spherical particles, 65-70nm diameter.
Capsid: 240 monomers, icosahedral, T=4.
Envelope: 80 trimer spikes, each spike = 3 x E1/E2 heterodimers, T=4

Genome:

Single-stranded, (+)sense, non-segmented RNA, ~11.7kb, 4-8% total weight of particle. Resembles cellular mRNAs: i.e. 5' cap, 3' poly-A:

Arbovirus genomes
Togavirus particle

 

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Replication:

Characteristically, there are two rounds of translation:

  1. (+)sense genomic RNA ('49S' = 11.7kb) acts directly as mRNA and is partially translated (5' end) to produce NS proteins.
  2. These proteins are responsible for replication, forming a complementary (-)strand, the template for further (+)strand synthesis.
  3. Two species of (+) RNA are synthesized, full length genomic RNA and sub-genomic mRNA ('26S' = 4.1kb).
  4. Translation of the newly synthesized sub-genomic RNA results in production of structural proteins (from 3' end of genome).
  5. Assembly occurs at the cell surface, and the envelope is acquired as the virus buds from the cell. Release and maturation almost simultaneous.

Replication occurs in the cytoplasm and is rapid (~4h c.f. 20-30h for Flaviviruses). Cellular receptors are not known - obviously widely distributed. Glycoprotein spikes are responsible for receptor binding - antisera neutralize attachment.

Togavirus replication

Pathogenesis:

Host Range: Broad, grow in both mammalian and insect cell lines, characteristically producing c.p.e. in the former but not the latter (mechanism unclear). Only Alphaviruses are arthropod-borne.
Pathogenesis: Virus is transmitted from the salivary glands of the mosquito to the bloodstream of the vertebrate host. Virus travels to the skin and reticuloendothelial system (spleen and lymph nodes), where the primary infection occurs, then viraemia follows - systemic infection. Can involve CNS (esp. encephalitis), skin/bone marrow/blood vessels (haemorrhagic fevers). Not well understood.
Treatment: A few experimental vaccines, none commonly in use.

Rubella virus:

One species, quite distinct from Alphaviruses. Limited host range - mammalian cells only. First recognized as a distinct disease in 1814 (as opposed to Measles/Scarlet fever). Association with congenital abnormalities recognized by Gregg 1941 (epidemic of congenital cataracts) - the first recognition of a virus as a teratogenic agent (i.e. capable of disrupting normal foetal development). Virus isolated in 1962. Similar to other Toga's, but slightly smaller (particle 60-70nm; genome ~11kb).

Host Range/Transmission: Can grow in a variety of mammalian cells. No known invertebrate host - man is the only reservoir, hence this virus is targeted by W.H.O. for eradication. Transmitted by aerosols - highly contagious.

Pathogenesis: Adult infections frequently sub-clinical! Characteristic pink, continuous maculopapular rash appears in 95% of adolescent patients 14-25 days (av. 18d) after infection - patient is infectious for most of this time. After early viraemia, virus multiplies in many organs, particularly lymph nodes (lymphadenopathy), including the placenta, but symptoms in adults are rare. In children, a mild febrile illness - less severe than measles. Virus crosses placenta and multiplies in the foetus. Up to 85% of infants infected in the first trimester of pregnancy get congenital rubella syndrome (CRS) - low birth weight, deafness, CNS involvement, abortion. The earlier in pregnancy infection occurs, the worse.

During 1964 and 1965 a rubella epidemic in the United States caused an estimated 12.5 million cases of rubella and 20,000 cases of congenital rubella syndrome which led to more than 11,600 babies born deaf, 11,250 fetal deaths, 2,100 neonatal (newborn) deaths, 3,580 babies born blind and 1,800 babies born mentally retarded - the last major epidemic in the USA (pre-vaccine). The foetus is persistently infected (presumably due to immature immune response) and continues to excrete virus after birth - a risk to doctors, nurses and other patients.

Prevention/Control: A live attenuated vaccine has been used in the USA since the late 1960's and more recently in the UK (as MMR). For women infected during first trimester of pregnancy, therapeutic abortion may be recommended.
MMR vaccine & autism.

Rubella and CRS

CDC recently claimed that rubella has been eliminated from the USA. CDC estimates that 93 percent of the nation's children younger than 2 receive the MMR vaccine. In the UK in 2004, more than 88% of infants were been given the vaccine - a 1.5% rise on 2003.

UK Department of Health current vaccination guidelines

Chikungunya, an epidemic arbovirosis
Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus was first isolated in 1953 in Tanzania. Chikungunya virus is a member of the genus Alphavirus and the family Togaviridae. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia. The word chikungunya, used for both the virus and the disease, means "to walk bent over" in some east African languages, and refers to the effect of the joint pains that characterise this dengue-like infection. Chikungunya is a specifically tropical disease, but it is geographically restricted and outbreaks are relatively uncommon. It is only occasionally observed in travellers and military personnel. More than 266 000 people have been infected during the ongoing outbreak in Réunion, in which Aedes albopictus is the presumed vector. In the ongoing Indian outbreak, in which Aedes aegypti is the presumed vector, 1 400 000 cases of chikungunya were reported during 2006. The reasons for the re-emergence of chikungunya on the Indian subcontinent, and for its unprecedented incidence rate in the Indian Ocean region, are unclear. Plausible explanations include increased tourism, chikungunya virus introduction into a naive population, and viral mutation.
Lancet Infect Dis. 2007 7: 319-327.

MicrobiologyBytes: Chikungunya

 


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