TogaViruses Characteristics

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TogaViruses - Characteristics

• enveloped, positive sense, single stranded RNA
• RNA serves as the m-RNA
• encodes early (nonstructural) and late
  (structural) proteins
• genome encodes the viral RNA dependent RNA
  polymerase
• replicate in the cytoplasm and bud through the
  cell membrane
• two genera pathogenic in humans Alphavirus and
  Rubivirus
• Alphaviruses Arboviruses
• same as above, but possess viral encoded envelope
  glycoproteins
• antigenic variation among glycoproteins
  distinguished one alphavirus from another
• capsid proteins on alphaviruses are similar in
  structure and cross-react antigenically
• broad host range forms the basis for many
  zoonoses
• all are Arthropod Borne Virues (ARBO)
• Rubivirus
• a togavirus which is similar to alphavirus, but
  possesses it own unique envelope glycoproteins
  which do not cross-react with other togaviruses

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TogaViruses Viral Cycle

• Adsorption
• each virus has specific host cell receptors to
  which its glycoproteins bind
• thus each virus has a different host range basis
  on glycoprotein affinity
• Penetration
• alphaviruses enter their host cells by
  receptor-mediated endocytosis
• the viral envelope fuses with the endosomal
  membrane
• this releases the capsid and genome into the
  cytoplasm
• Uncoating
• Capsid is removed by cytoplasmic enzymes

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TogaViruses Viral Cycle

• Transcription and Replication
• the alphavirus cycle is similar to picornaviruses
• viral RNA binds to the ribosomes as the m-RNA
• translated into an early polyprotein from
  two-thirds of the genome
• protease cleaves the polyprotein into four
  nonstructural proteins one of which is the RNA
  dependent RNA polymerase
• the polymerase catalyzes the synthesis of a full
  length negative sense template
• many positive sense RNA strands are formed from
  the template
• a small 26S m-RNA is synthesized from the
  negative sense template
• this is translated into late capsid and envelope
  proteins
• product of the late polyprotein are
• C protein capsid protein
• Envelope glycoproteins, E1, E2, E3, which are
  acetylated with long chain fatty acids in the
  endoplasmic reticulum and Golgi and transferred
  to the host cell membrane

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TogaVirus Virus Cycle

• Assembly
• The C proteins associate with the new RNA
  replicas and bind them to areas of the cell
  membrane which express the viral glycoproteins
• Release
• Alphaviruses are released when they bud through
  the host cell membrane and acquire the envelope
• RubiVirus The same

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TogaViruses - Pathogenesis

• Cellular Pathogenesis basis of cell death
• large amount of viral RNA blocks the cellular
  m-RNA from binding to the ribosome viral m-RNA
  may composed 90 of RNA in the cell
• this favors translation of viral m-RNA thus the
  decrease in cellular protein synthesis prevents
  the cell from maintaining itself cell death

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TogaViruses - Clinical Diseases

• AlphaVirus
• Viral Encephalities influenza-like
  symptoms(fever, chills, headaches, backache,
  rash) with viremia progressing to involve the
  CNS, esp the brain
• primary viremia from arthropod bite replication
  in the reticuloendothelial system resulting in
  secondary viremia
• if viral load in secondary viremia is great,
  viruses cross the blood brain barrier into the
  CNS
• Equine Encephalitis
• RubiVirus

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AlphaViruses - Encephalities

• Equine Encephalities
• Eastern Equine Encephalitis (EEE)
• Western Equine Encephalitis (WEE)
• Venezuelan Equine Encephalitis (VEE)
• Non-Equine Diseases

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TogaViruses Clinical Disease

• Rubivirus
• Rubella or German Measles
• Mild acute disease of children consisting of mild
  fever, swollen glands (lymphadenopathy), viremia,
  and a three day rash (exanthem)
• infection is more severe in adults causing bone
  and joint pain
• Rubivirus is not cytolytic and has only one
  serotype
• cell-mediated immunity and hypersensitivity
  contribute to severity
• major cause of teratogenesis which makes it a
  significant congenital disease
• in the absence of antibody during pregnancy, the
  virus replicates in the placenta, spreads to the
  fetal circulation, and infects most of the
  tissues in the developing fetus
• the virus alters normal cellular growth, mitosis,
  and chromosomal structure (teratogenesis)
• the virus persists in some tissues for 3 - 4 year
  following birth and causes immune tolerance
• fetus is a risk until the twentieth week of
  pregnancy
• Infants born exhibit congenital rubella syndrome

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RubiVirus Congenital Rubella Syndrome

• Classical triad of congenital disease
• Cataracts
• Cardiac abnormality
• Deafness
• Other manifestations
• Growth retardation
• Mental retardation

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TogaViruses - Epidemiology

• AlphaViruses
• Reservoir Wild Birds
• Transmission bird-to-Human, indirect,
  arthropod-borne, mosquitoes
• Equine Encephalities Horses are the most
  susceptible accidental hosts
• Humans are also accidental hosts
• EEE is the most virulent greatest mortality
• WEE is most common in the midwest mortality lt
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• Rubivirus
• Reservoir infected humans
• Symptomatic and asymptomatic carriers
• Transmission person-to-person, direct,
  respiratory droplet
• Current Incidence Rate ???

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TogaViruses - Control

• AlphaViruses
• Environmental reduction in mosquito populations
• Insecticides and larvicides
• Reduce human contact with mosquitos
• Mosquito traps and insect sprays
• Rubivirus
• Isolation of infected individuals esp. children
• Immunization
• Active attenuated Rubivirus antigen
• Recommended for all children and susceptble
  non-pregnant adult females

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FlaviViruses - Characteristics

• same structure as with Alphaviruses but somewhat
  smaller in size ( 40 nm)
• The major difference is in the organization of
  the genome and mechanism of protein synthesis
  only one long polyprotein
• Flaviviruses acquire their envelope as they bud
  into intracellular membranes (golgi/ER) and not
  from the cell membrane
• release is by exocytosis or lysis
• all Flaviviruses are serologically related
  antibody against one may neutralize the other.
• All Flaviviruses are Arthropod Borne Viruses
  (ARBOViruses)

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FlaviViruses - Pathogenesis

• Viral cycle is similar to TogaViruses exceptions
  noted previously
• Cellular Pathology
• same as with alphaviruses
• primary target cells are of the
  marcophage-monocytes lineage which express Fc
  receptors these receptors bind non-neutralizing
  antibody against the viruses and promotes their
  uptake into the cells T-cell which express these
  receptors are activated and release cytokines
  which weaken the vasculature causing bleeding,
  hemorrhage, and loss of plasma hemorrhagic fever

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FlaviViruses Clinical Diseases

• ARBOviruses
• Viral Encephalitis
• St. Louis Encephalitis
• West Nile Encephalitis
• Japanese B Encephalitis
• Hemorrhagic Fever
• Dengue Fever
• Yellow Fever
• Hepatitis C
• Hepacivirus

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FlaviViruses - Epidemiology

• ARBOviruses - Encephalitiies
• Reservoirs birds and small mammals, in some
  cases reptiles and amphibians
• Arthropod Vectors mosquitoes
• Rubrivirus
• Reservoir infected humans
• Mode-of-Transmission p-p, direct, respiratory
  droplet
• Hepacivirus
• Reservoir infected humans
• Mode of Transmission p-p, direct, blood/body
  fluids

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West Nile Encephalitis

• Symptoms
• Fever and/or meningoencephalitis
• 80 of cases are asymptomatic or only mild fever
• All patients have viremia most have fever and
  lymphadenopathy
• Epidemiology
• Reservoir Wild Birds esp. crows
• Transmission animal-to-person, direct,
  arthropod-borne, mosquitoes
• Currently, the leading cause of arboviral
  encephalitis in the U.S
• Fatalites occur mostly in elderly people (3 15
  mortality rate)

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St. Louis Encephalitis

• Symptoms
• Fever, headache, malagia in neck and back
• Epidemiology
• Most common cause of epidemic encephalitis in
  North America
• Approx. 130 confirmed cases annually in U.S
• Reservoir Wild Birds
• Transmission animal-to-person, indirect,
  arthropod-borne, Culex mosquitoes
• Fatalities 3-10 of cases

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Hemorrhagic Fever

• Yellow Fever
• Dengue

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Yellow Fever

• Acute febrile illness
• Rapid onset of fever, chills, headache,
  dizziness, myalgia
• Followed by nausea, vomiting, and bradycardia
• Progresses to jaundice, renal failure, and
  systemic hemorrhage
• Vomitus is black with clotted blood
• Patient die from renal failure 20 mortality
  rate
• Severe manifestation occur in about 15 of cases
• Patient is viremic during the entire disease
  course
• Pathogenesis
• Virus infects and its replicated by cells
• Lymph nodes, liver, spleen, kidney, bone marrow,
  and myocardium
• Most severe lesion occur in liver and kidney

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Yellow Fever

• Diagnosis
• Antigen detection from blood
• After fourth day symptoms
• Antibody during first week
• Virus specific IgM
• Epidemiology
• Urban (domestic) Yellow Fever
• Human Reservoir
• Transmission person-to-person, indirect,
  arthropod-borne
• Vectro Aedes aegyticus ( most famous mosquito)
• Jungle (sylvatic) Yellow Fever
• Wild Primate Reservoir mostly monkeys
• Transmission animal-to-animal, indirect,
  arthropod-borne
• Animal-to-person, indirect, arthropod-borne
• Vector various Aedes or Haemagogus mosquitos

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Yellow Fever - Control

• Reduce exposure to mosquito vectors
• Anti-mosquito chemicals
• Mosquito Netting
• Immunization
• Active attenuated virus vaccine
• Strain 17D of yellow fever virus has lost its
  trophism for viscera and nerves
• Virus is genetically modified and grown in eggs
• Has been used successfully for 70 years

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Dengue Fever