Teratogenicity of the Semliki Forest Virus Mutant ts22 for the Foetal Mouse: Induction of Skeletal and Skin Defects

Mabruk, Mohamed; Flack, Aksel; Glasgow, Gwendoline M.; Smyth, J; Folan, J. C.; Bannigan, John; O’Sullivan, Matthew L.; Sheahan, B. J.; Atkins, Gregory J.

doi:10.1099/0022-1317-69-11-2755

Cited by 19 publications

(16 citation statements)

References 13 publications

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“…The A7 ts22 mutant is teratogenic, inducing skeletal, skin, and neural tube defects in developing fetuses (Mabruk et al, 1988(Mabruk et al, , 1989. This is of interest given the teratogenic effects of the related rubella virus.…”

Section: Neuroinvasion Cns Tropism and Age-related Virulencementioning

confidence: 98%

Pathogenesis of Semliki Forest Virus Encephalitis

Fazakerley¹

2002

J. of Neurovirology

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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.

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Section: Neuroinvasion Cns Tropism and Age-related Virulencementioning

confidence: 98%

Pathogenesis of Semliki Forest Virus Encephalitis

Fazakerley¹

2002

J. of Neurovirology

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“…e central nervous system contained only small amounts of viral antigen and nucleic acid. It is proposed that the skeletal and skin defects induced in mouse foetuses by ts22 infection result from the tropism of the virus for mesenchymal cells involved in the development of such tissue [98]. Damage to the neural tube, including open neural tube defects, was detected in foetuses following infection of the mother at days 8 and 10 of pregnancy with both A7 and ts22.…”

Section: Foetal Infectionmentioning

confidence: 99%

The Pathogenesis of Alphaviruses

Atkins

2013

ISRN Virology

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Alphaviruses are enveloped single-stranded positive sense RNA viruses of the family Togaviridae. e genus alphavirus contains nine viruses, which are of medical, theoretical, or economic importance, and which will be considered. Sindbis virus (SINV) and Semliki Forest (SFV), although of some medical importance, have largely been studied as models of viral pathogenicity. In mice, SINV and SFV infect neurons in the central nervous system and virulent strains induce lethal encephalitis, whereas avirulent strains of SFV induce demyelination. SFV infects the developing foetus and can be teratogenic. Venezuelan Equine Encephalitis virus, Eastern Equine Encephalitis virus, and Western Equine Encephalitis virus can induce encephalitis in horses and humans. ey are prevalent in the Americas and are mosquito transmitted. Ross River virus, Chikungunya virus (CHIKV), and O'nyong-nyong virus (ONNV) are prevalent in Australasia, Africa and Asia, and Africa, respectively. ONNV virus is transmitted by Anopheles mosquitoes, while the other alphaviruses are transmitted by culicine mosquitoes. CHIKV has undergone adaptation to a new mosquito host which has increased its host range beyond Africa. Salmonid alphavirus is of economic importance in the farmed salmon and trout industry. It is postulated that future advances in research on alphavirus pathogenicity will come in the �eld of innate immunity.

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“…This was based on the method described previously for fetal tissue sections (Mabruk et al, 1988), using the methods of Holgate et al (1983) andSpringall et al (1984). For IGSS with anti-GC serum, treatment with Tween 80 was omitted.…”

Section: Immunogold-silver Stainingmentioning

confidence: 99%

“…For IGSS with anti-GC serum, treatment with Tween 80 was omitted. The anti-SFV antiserum, together with the corresponding pre-immune serum, was the polyclonal rabbit IgG described previously (Mabruk et al, 1988), and used .at a dilution of 1/80. Western blotting showed that this antiserum contained antibodies to all the viral structural proteins and some nonstructural proteins.…”

Section: Immunogold-silver Stainingmentioning

confidence: 99%

Pathogenicity of Semliki Forest virus for the rat central nervous system and primary rat neural cell cultures: possible implications for the pathogenesis of multiple sclerosis

Atkins

Sheahan

Mooney

1990

Neuropathology Appl Neurobio

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The neurovirulent L10 strain of Semliki Forest virus (SFV) causes extensive neuronal damage in the central nervous system (CNS) of infected rats, and is probably the cause of death. The avirulent A7 and M9 strains do not cause extensive neuronal damage, but do induce immune-mediated CNS demyelination. In primary CNS cell cultures derived from rats, L10 multiplies more rapidly in neurons than avirulent strains, but infection with both virulent and avirulent strains causes depletion of oligodendrocytes from mixed glial cell cultures. It is proposed that the immune-mediated demyelination, which follows infection with avirulent strains, is induced by phagocytosis of myelin debris from infected oligodendrocytes, and the presentation of antigens derived from such debris to T-helper lymphocytes. Based on these and previous results, a scheme for the pathogenicity of defined strains of SFV is proposed. The applicability of this scheme to the understanding of human demyelinating disease such as multiple sclerosis is discussed.

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Teratogenicity of the Semliki Forest Virus Mutant ts22 for the Foetal Mouse: Induction of Skeletal and Skin Defects

Cited by 19 publications

References 13 publications

Pathogenesis of Semliki Forest Virus Encephalitis

Pathogenesis of Semliki Forest Virus Encephalitis

The Pathogenesis of Alphaviruses

Pathogenicity of Semliki Forest virus for the rat central nervous system and primary rat neural cell cultures: possible implications for the pathogenesis of multiple sclerosis

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