Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion - PubMed (original) (raw)

Review

Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion

Melanie A Samuel et al. J Virol. 2006 Oct.

No abstract available

Figures

FIG. 1.

E16 contact residues and binding of WNV virions. (A) E16 contact residues (red) on DIII of the WNV envelope protein are located in the amino terminus (residues 302 to 309) and three strand-connecting loops, BC (residues 330 to 333), DE (residues 365 to 368), and FG (residues 389 to 391). (B) Pseudoatomic model of the cryoelectron microscopic reconstruction of the WNV virion. The E16 structural epitope is mapped in magenta. (C) Saturation binding of E16 on the WNV particle. E16 is predicted to bind 120 out of 180 potential epitopes with exclusion from the inner fivefold axis. (D and E) Magnified regions of the boxed areas in panel C. This figure is reprinted with permission from Macmillan Publishers Ltd. (Nature **437:**764-768, copyright 2005).

FIG. 2.

WNV dissemination and immune system control. (A) WNV is maintained in nature in an enzootic mosquito-bird-mosquito transmission cycle. (B) Following Culex mosquito inoculation, WNV replicates in skin Langerhans dendritic cells, which traffic the virus to the lymph node, where further replication ensues. Following induction of a primary viremia, WNV spreads to other peripheral organs. Several aspects of the innate and adaptive immune response limit WNV replication in the periphery. IFN-α/β acts as an antiviral agent that restricts viral translation and replication soon after infection. B cells and antibody (primarily IgM) modulate viral levels in serum and prevent early CNS seeding, while complement is required for efficient priming of humoral and cellular immune responses. IFN-γ-secreting γδ T cells control viral replication through direct antiviral mechanisms and contribute to the generation of adaptive immune responses. CD4+ and CD8+ T cells participate in viral clearance from peripheral tissues. (C) Following replication in the periphery, WNV spreads to the CNS possibly through TNF-α-mediated changes in BBB permeability. Neurons are the primary target of WNV in the brain and spinal cord. IFN-α/β is required to control WNV infection in the CNS and may prolong neuronal survival. The chemokines CXCL10 and CCL5 and their cognate ligands CXCR3 and CCR5 aid in recruiting CD4+ and CD8+ T cells and monocytes to the CNS, where they function to clear virus from infected tissues.

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Pathogenesis of West Nile Virus infection: a balance between virulence, innate and adaptive immunity, and viral evasion - PubMed (original) (raw)