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Togaviruses


VIRUS:
  • Togaviruses: Alphavirus, Flavivirus


GENERAL CONCEPTS:
  • The Togaviruses are divided into two groups; Alphaviruses and Flaviviruses.
  • Togaviruses are enveloped and contain a positive stranded RNA genome. This RNA is 5'-capped and 3'-polyadenylated.
  • This group of viruses are called "arboviruses" because their life cycle involves alternating between vertebrates and arthropod vectors, mostly mosquitoes.
  • The Togavirus' natural cycle usually involves birds and mammals and rarely humans with the exception of those responsible for yellow fever and dengue fever.
  • Overall, there are approximately 25 types that are pathogenic for humans.


DISTINCTIVE PROPERTIES:
  • Alphaviruses: Members of this group contain a nucleoprotein capsid surrounded by a lipid bilayer envelope that is derived from the host cell membrane plus two 50 kD glycoproteins. Their RNA is 4 x 106 daltons and the capsid is composed of a single 30 kD capsid protein. Antibodies specific for the glycoproteins are neutralizing. The viruses enter host cells by pinocytosis and they replicate in the cytoplasm. Translation of the genomic RNA gives a large polyprotein that is cleaved to yield an RNA polymerase and the structural proteins. Once assembled, the progeny virions bud from the host cell, picking up their envelope.
  • Flaviviruses: This group is very similar to the Alphavirus group with a few exceptions. First, the genomic RNA is not polyadenylated until it enters the host cell. Second, the single capsid protein is smaller (14 kD). Third, the completed virion forms in the cytoplasm in association with the endoplasmic reticulum instead of budding from the cell.


PATHOGENESIS:
  • Alphaviruses: There are three agents that cause disease in humans;
    1. Chikungunya: This disease is transmitted by a mosquito, resulting in viremia that presents as an acute, febrile illness with malaise, a rash and arthritis.
    2. Eastern and Western Equine Encephalitis (EEE, WEE): Following the bite of an infected mosquito, the resultant viremia is often asymptomatic. However, if the virus invades neural tissue, encephalitis may result. This condition is marked by high fever, delirium, coma and possibly death due to convulsions and paralysis.
    3. Venezuelan Equine Encephalitis (VEE): Similar to EEE and WEE, VEE has more systemic manifestations with less neural involvement.

  • Flaviviruses: There are four agents that cause disease in humans;
    1. St. Louis Encephalitis (SLE): Transmitted by mosquitos, a viremia occurs but in most cases no disease results. In some, however, central nervous system involvement gives inflammation and neuronal degeneration, clinically presenting with fever, headache, convulsions, coma and death.
    2. West Nile Encephalitis (WNE): WNE is very similar to SLE and it is also transmitted by mosquitos. In most cases no disease results. Mild, flu-like cases may be referred to as "West Nile fever". More severe cases of "West Nile encephalitis" or "West Nile meningitis" indicate central nervous system involvement that can lead to death
    3. Yellow fever: This is a severe systemic disease (unlike SLE). The virus replicates in reticuloendothelial (RE) cells in many organs, producing liver damage and intestinal hemorrhages. Typically, phase 1 presents with a fever, headache, nausea and vomiting, while phase 2 shows toxicity, jaundice, shock and death.
    4. Dengue fever and Dengue Hemorrhagic fever: The virus producing these diseases initially replicates in the skin at the site of the mosquito bite. Next, lymph nodes and the RE system become involved and viremia results. Fever and rash lasting 3-9 days defines the symptomology. Dengue fever is usually self-limiting but Dengue Hemorrhagic fever often involves additional processes (probably immunopathologic) that produce extreme vascular permeability, shock and death.


HOST DEFENSES:
  • Togaviruses induce interferon and are susceptible to its effects. Infections usually resolve once antiviral antibody is produced. The role of the cell-mediated response is less well known but is probably important.


EPIDEMIOLOGY:
  • Alphaviruses are generally associated with birds and horses and their mosquitoes. Flaviviruses are generally associated with birds and bird-feeding mosquitoes for SLE and WNE. Yellow fever and Dengue fever are human in origin.


DIAGNOSIS:
  • Clinical: The epidemiology of the infection along with clinical suspicion and laboratory results are diagnostic.
  • Laboratory: One can isolate the virus from the blood during the viremic phase.


CONTROL:
  • Sanitary: Surveillance and vector control are excellent means for disease prevention.
  • Immunological: A live vaccine against Yellow fever and killed vaccines against EEE and WEE are available for those at high risk.
  • Chemotherapeutic: None available.

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