About the Virus

Viral Structure

  • West Nile Virus is a neutropic flavivirus from the Flaviviridae family
  • Related to dengue viruses, yellow fever viruses and Japanese encephalitis viruses
  • Enveloped
  • Single stranded, positive sense RNA viruses, approximately 11 Kb in length
  • Polycistronic, where the genome is translated as a single polypeptide that is later cleaved by host and viral proteases into structural and non-structural proteins

    A) Structural Proteins

  • Capsid (C) protein: binds viral RNA
  • Premembrane (prM) protein: blocks premature viral fusion and may chaperone envelope (E) protein folding
  • Envelope (E) protein: mediates viral attachment, membrane fusion and viral assembly

    B) Non-structural Proteins

  • NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5: regulate viral transcription and replication and attenuate host antiviral responses

    Basic Life Cycle

    Attachment Molecules for Binding

  • DC-SIGN, DC-SIGN-R, and integrin αvß3
  • Attachment receptors in vivo for physiologically important cell types, such as neurons, remain uncharacterized

    1) Entering the Cell

  • Virus enters cells via receptor-mediated endocytosis that may involve clathrin-coated pits → pH-dependent conformational change in the E protein → viral and endosomal membranes fuse → release of viral nucleocapsid into the cytoplasm

    2) Replication

  • Virus replicate on endoplasmic reticulum-associated membranes to generate a negative-strand RNA intermediate → template for nascent positive-strand RNA synthesis → Positive-strand RNA is either packaged within progeny virions or used to translate additional viral proteins

    3) Leaving Cell

  • Virus assembles and buds into the endoplasmic reticulum as immature particles that contain the prM protein → transported through the trans-Golgi network → furin-mediated cleavage of prM to M generates mature, infectious virions → released by exocytosis

    Viral Dissemination and Pathogenesis in vivo

  • Peripheral inoculation → initial replication in skin Langerhans dendritic cells → migrate to and seed draining lymph nodes → primary viremia → infection of peripheral tissues (spleen and kidney)
  • End of the first week: WNV is largely cleared from the serum and peripheral organs and infection of the CNS is observed in a subset of immunocompetent animals
  • Virus is cleared from all tissue compartments within 2 to 3 weeks after infection
  • Infection is not significantly detected in non-neuronal CNS cell populations in humans or animals
  • Persistent infection: immunosuppressed patient in whom viremia was detected for more than 60 days
  • Avian hosts: the virus has been detected by histology, reverse transcription-PCR, and virologic assays in the brains, livers, lungs, spleens, hearts, and kidneys of naturally infected crows and blue jays; pathogenesis unknown

    Crossing the Blood Brain Barrier (BBB)

  • Tumor Necrosis Factor alpha (TNF-α)-mediated changes in endothelial cell permeability may facilitate CNS dissemination via hematogenous spread
  • “Trojan horse” mechanism in which the virus is transported by infected immune cells that traffic to the CNS
    Hayes, EB. et al. (2005) Virology, pathology, and clinical manifestations of West Nile Virus disease. Emerg Infect Dis. 11(8):1174-9.


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    Image From:
    Rendelman, Brad. The Cycle. Digital image. Southern 7 Health Department and Head Start. Illinois Department of Public Health, n.d. Web. [http://www.southern7.org/west-nile-faq.html].