Yellow fever virus

Noreen A. Hynes, M.D., M.P.H., D.T.M.&H.
Yellow fever virus is a topic covered in the Johns Hopkins ABX Guide.

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MICROBIOLOGY

  • Yellow fever virus (YFV) is the prototype member of the approximately 75 viruses of Flaviviridae family; "flavus" derives from the Latin word for yellow.
    • Mosquito vector
    • YFV first isolated in 1927.
  • There is 1 serotype with 7 distinct genotypes.[7]
    • South America: 2 genotypes
    • Africa: 5 genotypes
  • Single-stranded RNA virus with an 11 kilobase genome composed of 3 parts:[2]
    • 5’ non-coding region
    • a single open reading frame (ORF) which encodes 3 structural and 7 non-structural proteins
      • Structural
        • Capsid (C)
        • Membrane (prM)
        • Envelope (E): This is the main structural protein
          • Mediates virus entry into the cell via clarathrin-dependent endocytosis
      • Non-Structural (NS): NS1, NA2a, NS2b, NS3, NS4a, NS4b, and NS5 are involved in:
        • RNA replication
        • Post-translational clevage of the viral polyprotein
    • 3’ non-coding region
  • Cell targets
    • Virus introduced by blood-feeding mosquito into the epidermis where resident dendritic cells (DC) are the principle target for early virus replication.[3]
      • Toll-like receptors (TLRs) on the surface of DC are key in the critical role of sensing microbial stimuli.
      • DCs initiate and modulate the adaptive immune system.
    • DCs carry the virus via lymphatics to draining lymph nodes and subsequently to the bloodstream with eventual dissemination to cells in the liver, spleen, remaining lymph nodes, kidneys and heart.[7]
  • Immune evasion[2]
    • Inhibition of the innate interferon type I response is key
    • Non-human primate studies have demonstrated down-regulation of 43 genes associated with innate immunity, including
      • Interferon gamma receptor-1
      • CD83, a marker of DC maturation
      • TNFSF11: though to induce DCs to stimulate naive T cell proliferation
  • Inflammation
    • Pro-inflammatory mediators are significantly higher in patients with fatal illness when compared with survivors[2] including:
      • Tumor necrosis factor-alpha (TNF-α)
      • Interleukin-6 (IL-6)
      • Interleukin-1 receptor antagonist (IL-1RA)
      • Interferon-gamma inducible protein 10 (IP-10)
      • Monocyte chemoattractant protein-1 (MCP-1)
    • Similar findings were seen in rhesus macaques, the animal model for studying many aspects of yellow fever virus infection

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Last updated: September 25, 2016