title: Pathogenesis of Semliki Forest virus encephalitis.
abstract: This article provides a review of the pathogenesis of Semliki Forest virus (SFV) encephalitis. In mice, outcome of infection varies according to age of the mouse and strain of the virus and can include acute encephalitis, subacute demyelinating meningoencephalomyelitis, and persistent subclinical central nervous system (CNS) infection. All strains of virus are virulent in mice infected <12 days of age. The L10 strain is also virulent in mice >14 days age, whereas the A7(74) strain is avirulent. The genetic difference between these strains maps to the nsp3 gene. For A7(74) virus, age-related virulence correlates with ability of CNS neurons to replicate virus and undergo apoptotic cell death. Immature developing neurons support complete virus replication but as neuronal populations and circuits mature in the postnatal brain, virus infection becomes progressively restricted and nonproductive. This restricted replication can be overcome by gold I compounds, which may function by inducing neuronal dedifferentiation to a state permissive for virus replication. Biochemical pathways associated with membrane biogenesis may be an important determinant of this effect. Infection of some developing neuronal populations results in apoptosis, whereas infection of mature neurons results in persistent infection. An active type-I interferon system prevents virus spread in extraneural tissues. An initial high-titer plasma viremia is controlled by immunoglobulin M (IgM) antibodies. Virus enters the brain across cerebral endothelial cells and initiates scattered foci of perivascular infection. The blood-brain barrier is disrupted. Neurons and oligodendrocytes are the cell types most frequently infected. Infectivity in the brain can be eliminated by IgG antibodies, though an active T-cell response is required for virus elimination. Lesions of inflammatory demyelination require the presence of CD8(+) T lymphocytes and probably result from destruction by these cells of virally infected oligodendrocytes.
authors.affiliation: Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, United Kingdom. John.Fazakerley@ed.ac.uk
authors.forename: John K
authors.initials: JK
authors.lastname: Fazakerley
mesh_terms: D018354:Alphavirus Infections / Q000209:etiology* / Q000276:immunology / Q000821:virology; D000818:Animals; D018792:Encephalitis, Viral / Q000209:etiology* / Q000276:immunology / Q000821:virology; D051379:Mice; D012672:Semliki forest virus