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 groupVirus group Human pathogensHuman pathogens

Togaviruses

Alphavirus

Rubivirus

Arterivirus

Flaviviruses

Flaviviridae

Hepaciviridae

Pestivirus

Arboviruses

Rubella virus

None

Arboviruses

Hepatitis C virus

None

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.

ArbovirusesDiseaseDisease VectorVector HostHost DistributionDistribution diseasedisease

AlphavirusesAlphavirusesSindbis

Semliki forest

Venezuelan equine enceph.

Eastern equine encep.

Western equine encep.

Aedes & other mosquitos

Aedes & other mosquitos

Aedes, Culex

Aedes, Culiseta

Culex, Culiseta

Birds

Birds

Rodents,horses

Birds

Birds

Africa,Australia,India

East and west Africa

North,South,&Central America

North&South America, Caribbean

North & South America

Subclinical

Subclinical

Mild systemic,severe encephal.

Mild systemic,encephal.

Mild systemic,encephal.

ArbovirusesDiseaseDisease VectorVector HostHost DistributionDistribution diseasedisease

AlphavirusesAlphavirusesChikungunya Aedes Humans,

MonkeysAfrica, Asia Fever,

Arthralgia, arthritis

ArbovirusesDiseaseDisease VectorVector HostHost DistributionDistribution diseasedisease

FlavivirusesFlavivirusesDengue

Yellow fever

Aedes

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

ArbovirusesDiseaseDisease VectorVector HostHost DistributionDistribution diseasedisease

FlavivirusesFlavivirusesJapanese encephalitis

West Nile encephalitis

St. Louis encephallitis

Russian spring-summer encephalitis

Powassan encephalitis

Culex

Culex

Culex

Ixodes & dermocentor ticks

Ixodes ticks

Pigs, birds

Birds

Birds

Birds

Small mammals

Asia

Afr.,Eur.,CentralAsia,N.Amer

N. America

Russia

N. America

Encephalitis

Fever, encep., hepatitis

Encephalitis

Encephalitis

Encephalitis

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 disesasehemorrhagic disesase can occur

Togaviruses & Flaviviruses/Clinical syndromes Hemorrhagic disesasesHemorrhagic disesases

Dengue Yellow fever viruses

Togaviruses & Flaviviruses/Clinical syndromes Hemorrhagic disesasesHemorrhagic 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 disesasesHemorrhagic disesases

Yellow fever viruses Severe systemic disease Degeneration of the liver, kidney, heart +

hemorrhages “JAUNDICEJAUNDICE” 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

1. The tissue affected

2. 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