Togaviruses and Flaviviruses

Unique features of Togaviruses & Flaviviruses Enveloped Positive sense ssRNA Togaviruses replicate in the cytoplasm and bud at the plasma membranes Flaviviruses replicate in the cytoplasm and bud at internal membranes

Togaviruses and Flaviviruses Virus group Human pathogens Togaviruses Alphavirus Rubivirus Arterivirus Flaviviruses Flaviviridae Hepaciviridae Pestivirus Arboviruses Rubella virus None Hepatitis C virus

Togaviruses and Flaviviruses Alphavirus and Flavivirus are discussed together because of similarities in the diseases that they cause, as well as in epidemiology. Most are transmitted by arthropods and are therefore arboviruses (arthropod-borne viruses). They differ in size, morphology, gene sequence, and replication.

Togaviruses and Flaviviruses The alphaviruses and flaviviruses: These viruses have a very broad host range, including vertebrates (e.g., mammals, birds, amphibians, reptiles) and invertebrates (e.g., mosquitoes, ticks). Diseases spread by animals or with an animal reservoir are called zoonoses.

Togaviruses Alphavirus, Rubivirus, and Arterivirus. No known arteriviruses cause disease in humans, so this genus is not discussed further. Rubella virus is the only member of the Rubivirus group; it is discussed separately, because its disease manifestation (German measles) and its means of spread differ from those of the alphaviruses.

Togaviruses and Flaviviruses The Flaviviridae include the flaviviruses, pestiviruses, and hepaciviruses (hepatitis C and G viruses). Hepatitis C and G are discussed inhepatitis viruses.

Arboviruses Disease Vector Host Distribution disease Alphaviruses Sindbis Semliki forest Venezuelan equine enceph. Eastern equine encep. Western equine encep. Aedes & other mosquitos Aedes, Culex Aedes, Culiseta Culex, Culiseta Birds Rodents,horses Africa,Australia,India East and west Africa North,South,&Central America North&South America, Caribbean North & South America Subclinical Mild systemic,severe encephal. Mild systemic,encephal.

Arboviruses Disease Vector Host Distribution disease Alphaviruses Chikungunya Aedes Humans,Monkeys Africa, Asia Fever, Arthralgia, arthritis

Arboviruses Disease Vector Host Distribution disease Flaviviruses Dengue Yellow fever Aedes Humans, Monkeys Humans, monkeys Worldwide,esp. Tropics Africa, South America Mild systemic; break-bone fever, dengue hemorrhagic fever, and dengue shock syndrome Hepatitis, hemorrhagic fever

Arboviruses Disease Vector Host Distribution disease Flaviviruses Japanese encephalitis West Nile encephalitis St. Louis encephallitis Russian spring-summer encephalitis Powassan encephalitis Culex Ixodes & dermocentor ticks Ixodes ticks Pigs, birds Birds Small mammals Asia Afr.,Eur.,CentralAsia,N.Amer N. America Russia Encephalitis Fever, encep., hepatitis

Togaviruses & Flaviviruses/Clinical syndromes Alphavirus disease is usually characterized as low-grade disease Can progress to encephalitis in humans Flavivirus infections are relatively benign Serious aseptic meningitis, encephalitis, hemorrhagic disesase can occur

Togaviruses & Flaviviruses/Clinical syndromes Hemorrhagic disesases Dengue Yellow fever viruses

Togaviruses & Flaviviruses/Clinical syndromes Hemorrhagic disesases Dengue virus Major worldwide problem 100 million cases of dengue fever/year 250 000 cases of dengue hemorrhagic fever/y Dengue shock syndrome

Togaviruses & Flaviviruses/Clinical syndromes Hemorrhagic disesases Yellow fever viruses Severe systemic disease Degeneration of the liver, kidney, heart + hemorrhages “JAUNDICE” Mortality rate: ~ 50% during epidemics

Togaviruses & Flaviviruses/Laboratory diagnosis Cell culture vertebrate and mosquito cell lines difficult IF, hemadsorbtion RT-PCR Serology ELISA HI LA

Togaviruses & Flaviviruses/Treatment, Prevention, and Control No treatment! “The easiest means of preventing the spread of any arbovirus is elimination of its vector and breeding grounds” Vaccines Yellow fever live vaccine (17D strain) EEE, WEE, Japanese, Russian SSE killed vaccines

Rubella virus Same structural properties and mode of replication as the other toga’s Rubella is a respiratory virus Does not cause readily detectable cytopathologic effects

Rubella One of the 5 classic childhood exantems Measles Roseola Fifth disease Chickenpox

Rubella Rubella: “little red” in Latin “German measles” Infects URT local lymphe nodes viremia Shedding respiratory droplets Only one serotype Natural infection lifelong protective immunity

Congenital Rubella “Serious congenital abnormalities in the child” If the mother does not have antibody The virus can replicate in most tissues of the fetus The normal growth, mitosis, and chromosomal structure of the fetus’s cells can be altered by the infection

Congenital Rubella The normal growth, mitosis, and chromosomal structure of the fetus’s cells can be altered by the infection Improper development of the fetus, small size of the infected baby, and the teratogenic effects

Congenital Rubella The nature of the disorder is determined by The tissue affected The stage of development disrupted

Congenital Rubella ~20% of women of childbearing age escape infection during childhood and are susceptible to infection unless vaccinated

Rubella/Clinical syndromes Rubella disease Normally benign 3 day of maculopapular or macular rash and swollen glands More severe in adults

Rubella/Clinical syndromes Congenital disease The fetus is at major risk until the 20th week of pregnancy Most common manifestations: Cataracts Mental retardation deafness

Rubella/Laboratory diagnosis Anti-Rubella IgM by ELISA Avidity test: Low avidity 4x increase in IgG Antibodies to rubella are assayed early in pregnancy to determine the immune status of the woman

Rubella/Treatment, Prevention, and Control No treatment Vaccination (live) MMR vaccine