Vector-Borne Viruses

Arboviruses

• Flaviviridae

  • West Nile

  • Dengue

  • Yellow Fever

  • Zika Virus

• Togaviridae

  • Hanta virus

  • Alphaviruses

    • Old world

      • Chikungunya

      •  Crimean-Congo hemorrhagic fever

    • New world

      •  Encephalitis

Vectors of Dengue and Chikungunya

Mosquito Transmission of Infectious Disease

Characteristics of Dengue

Dengue Virus

• 4 serotypes

• Emerged separately about 100 years ago

• Factors:

  • Deforestation

  • Urbanization

  • Water use

  • Loss of mosquito eradication programs

Symptoms Dengue Virus

• Few or no symptoms:  80%

• Mild fever

• High fever and pain

• Hemorrhagic fever

• Shock syndrome

Dengue Viral Proteins

• E– Envelop receptor binding protein (DC-Sign)

• NS2B/NS3– Protease

• NS5– RNA Dependent RNA Polymerase

• NS1– Increases viral replication

• sNS1—activates TLRs, increases inflammation, neuroinvasion

Dengue Viral Tropism

• Monocytes/macrophages

• Dendritic cells

• B and T leukocytes 

• Endothelial cells

• Bone marrow

• Hepatoma

• Neuroblastoma

• Kidney-derived cells

Antibody dependent enhancement

• Severity of dengue is increased significantly by pre-infection with another strain of dengue virus

• Production of cross-reactive antibodies

• Antibodies bind to receptors on immune system cells, aiding in viral entry

• Increases viral load

• Increased activation of memory T cells may also increase inflammation

Mechanism of disease

• Viral entry into multiple cells, especially macrophages

• Suppression of IFN- alpha, beta, and gamma response

• Activation of T cells to overproduce cytokines

• Cytokines bind endothelial cells, causing bleeding

• ADE increases entry into cells and memory T cell response

Zika virus

• First discovered in Uganda in 1947

• Local cases of disease

• Outbreak on Island of Yap, 2007

  • Rashs

  • Ocular pain

• Spread through Pacific Islands in 2000s

• Emerged as a cause of microcephaly in 2013 (French Polynesia) and 2015-present (Brazil and others)

Microcephaly

• Crosses placental barrier

• Infects placental trophoblasts and macrophages

• Causes placental inflammation

• Can grow in fetal neuronal tissue

• Added to TORCH (toxoplasma, other, rubella, cytomegalovirus, and herpes)

Mechanisms of Microcephaly

• Placental Insufficiency

• Inflammation

• Changes to blood vessel formation

• Direct neuronal infection

Transmission of Zika

• Mosquitoes

• Sexual Transmission

• Mother to fetus

Chikungunya

Viral Life Cycle

Small changes in E1 lead to increased transmission, change in vectors

Course of Disease

• Replicates in fibroblasts near the site of infection

• Replicates in lymphoid tissues, particularly in macrophages

• Moves to endothelial cells in liver, satellite cells, brain cells, and joint fibroblasts

Symptoms

• Symptomatic in most people

• Self-limiting fever (5-7 days) with muscle pain, hepatitis

• 2-3% of patients:  severe muscle pain continues intermittently (may be autoimmune)

• Rare:  encephalitis, hemorrhagic fever (primarily in neonates)