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TogaViruses Characteristics dengue fever

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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
      • 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 –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
            • the viral envelope fuses with the endosomal
            • this releases the capsid and genome into the
 • Uncoating
    – Capsid is removed by cytoplasmic enzymes
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
               • a small 26S m-RNA is synthesized from the negative
                 sense template
                    • this is translated into late capsid and envelope
               •    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
               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
• Release
   • Alphaviruses are released when they bud through the host cell
     membrane and acquire the envelope
   • RubiVirus – The same
          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
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
             • if viral load in secondary viremia is great, viruses
               cross the blood brain barrier into the CNS
                  • Equine Encephalitis
 • RubiVirus
         AlphaViruses - Encephalities
• Equine Encephalities
   – Eastern Equine Encephalitis (EEE)
   – Western Equine Encephalitis (WEE)
   – Venezuelan Equine Encephalitis (VEE)
• Non-Equine Diseases
     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”
 RubiVirus – Congenital Rubella Syndrome
• Classical triad of congenital disease
   • Cataracts
   • Cardiac abnormality
   • Deafness
• Other manifestations
   • Growth retardation
   • Mental retardation
              TogaViruses - Epidemiology
• AlphaViruses
   – Reservoir = Wild Birds
   – Transmission = bird-to-Human, indirect, arthropod-borne, mosquitoes
   – Equine Encephalities = Horses are the most susceptible accidental
   – Humans are also accidental hosts
      • EEE is the most virulent = greatest mortality
      • WEE is most common in the midwest = mortality < 7%
• Rubivirus
   – Reservoir = infected humans
      • Symptomatic and asymptomatic carriers
   – Transmission = person-to-person, direct, respiratory droplet
   – Current Incidence Rate = ???
                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
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)
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
        FlaviViruses – Clinical Diseases
• ARBOviruses
      • Viral Encephalitis
          – St. Louis Encephalitis
          – West Nile Encephalitis
          – Japanese B Encephalitis
      • Hemorrhagic Fever
          – Dengue Fever
          – Yellow Fever
• Hepatitis C
   – Hepacivirus
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
                 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,
   – Currently, the leading cause of arboviral encephalitis in the U.S
   – Fatalites occur mostly in elderly people (3 – 15% mortality rate)
                 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
           Hemorrhagic Fever
• Yellow Fever
• Dengue
                        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
      • Most severe lesion occur in liver and kidney
                        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
                  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
Dengue Fever

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