Replication of the A7(74) Strain of Semliki Forest Virus Is Restricted in Neurons

Fazakerley, John K.; Pathak, S.; Scallan, Martina F.; Amor, Sandra; Dyson, Heather

doi:10.1006/viro.1993.1414

Cited by 120 publications

(169 citation statements)

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“…21,22 As expected, no neurological deficits or altered behavior could be observed during the experiments in the present study, and the mice remained alert, ate and drank normally and did not lose weight.…”

Section: Presence Of Sfv A7(74) Virus In Nude Mouse Tumors and Brainsupporting

confidence: 84%

“…We expected no side effects in the present study as SFV A7 (74) is avirulent in both normal immunocompetent animals as well as in nude mice. 21,22 On the other hand, it was not clear whether the immune system would allow the virus enough time to successfully find and destroy the tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The decline in virus antigen observed in the present study correlates with peaking of virus-specific IgM and the leakiness of the bloodbrain-barrier that occurs during infection with avirulent SFV. 21,22,[24][25][26] We therefore believe that virus-specific IgM may have inhibited virus replication below the detection limit due to temporary access of serum components to the CNS. Although not analyzed in the present study, the A7(74) CNS titers have been shown to be restricted also in nude and SCID mice (several magnitudes lower than in WT SFV), indicating that the restriction of A7(74) replication is not mediated by cells of the adaptive immune system.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Määttä

Liimatainen

Wahlfors

et al. 2007

Intl Journal of Cancer

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Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p < 0.05) with one virus injection, but the tumor size continued to increase after a lag period and none of the treated animals survived. Three virus injections or T-cell suppression with dexamethasone did not significantly improve treatment efficacy. It appeared that the local virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested. ' 2007 Wiley-Liss, Inc.

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Section: Presence Of Sfv A7(74) Virus In Nude Mouse Tumors and Brainsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Määttä

Liimatainen

Wahlfors

et al. 2007

Intl Journal of Cancer

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“…The tropism of these two strains of virus for CNS cells is the same both in cell culture and in the animal ; oligodendrocytes and neurons are infected, whereas astrocytes are resistant to infection (Gates et al, 1985 ;Atkins et al, 1990 ;Smyth et al, 1990 ;Balluz et al, 1993 ;Fazakerley et al, 1993). The two strains do differ, however, in their rate of multiplication in the CNS (Balluz et al, 1993) and in cultured neurons (this study ; Gates et al, 1985 ;Atkins et al, 1990).…”

mentioning

confidence: 62%

“…Fax j353 1 6799294. e-mail gatkins!tcd.ie Sheahan, 1982 ;Gates et al, 1985 ;Atkins et al, 1990 ;Smyth et al, 1990 ;Balluz et al, 1993 ;Fazakerley et al, 1993). Demyelination is triggered by infection of oligodendrocytes, which occurs in both the animal (Atkins & Sheahan, 1982 ;Sheahan et al, 1983) and in cultured glial cells Gates et al, 1985 ;Atkins et al, 1990).…”

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confidence: 99%

Death mechanisms in cultured cells infected by Semliki Forest virus.

Glasgow

McGee

Sheahan

et al. 1997

Journal of General Virology

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We have investigated the induction of cell death in cultured cells by the virulent SFV4 and avirulent A7 strains of Semliki Forest virus (SFV). In BHK cells, death occurred by a typical apoptotic mechanism, as did the death of oligodendrocytes in glial cell cultures. For cerebellar neuron cultures, virusinduced death was due to necrosis. Although the SFV4 and A7 strains did not differ in the mechanism of induction of cell death, the virulent SFV4 strain did multiply to a higher titre in cultured neurons than the avirulent A7 strain. This is consistent with previous animal studies which indicate that the virulence of SFV strains is controlled by rapidity of multiplication in the CNS, leading to a lethal threshold of damage, rather than differential cell tropism or cell death mechanisms. The immunemediated demyelination induced by avirulent strains may be triggered by apoptosis of oligodendrocytes, the consequences of which are obscured by death for virulent strains.Cell death mechanisms are an important component of pathogenesis in virus infections, although the mechanisms of induction of cell death are not well understood. The fate of infected cells, especially cells of the central nervous system (CNS), is of critical importance to mortality and morbidity in virus disease. A number of animal models of virus neuropathogenesis have been investigated in an attempt to define events which determine virulence (Atkins et al., 1994).One such model is infection of mice and rats by the alphavirus Semliki Forest virus (SFV ; Atkins et al., 1985). SFV causes fatal encephalitis following infection by virulent strains and immune-mediated demyelination following infection by avirulent strains. Virulent strains grow to high titre in the CNS and induce fatal damage to neurons. In contrast, avirulent strains multiply slowly, causing less neuronal damage, and are cleared from the CNS by immune intervention (Atkins &

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Alphavirus‐Mediated Gene Transfer into Neurons

Ehrengruber

Lundström

2000

CP Neuroscience

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Semliki Forest virus and Sindbis virus belong to the alphavirus genus of the togaviruses and have recently been shown to efficiently infect neurons in vitro and in vivo, i.e., under conditions where glial cells are present. This unit describes the preparation and application of recombinant, neurotrophic replicons derived from Semliki Forest virus and Sindbis virus for gene transfer into hippocampal neurons.

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Replication of the A7(74) Strain of Semliki Forest Virus Is Restricted in Neurons

Cited by 120 publications

References 0 publications

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

Death mechanisms in cultured cells infected by Semliki Forest virus.

Alphavirus‐Mediated Gene Transfer into Neurons

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