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
    Citation:
    Hayes, EB. et al. (2005) Virology, pathology, and clinical manifestations of West Nile Virus disease. Emerg Infect Dis. 11(8):1174-9.

    Transmission

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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].

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