Death mechanisms in cultured cells infected by Semliki Forest virus.

Abstract

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 &

Potent therapeutic efficacy of an alphavirus replicon DNA vaccine expressing human papilloma virus E6 and E7 antigens

“…28 The type I IFN response induces T cell memory responses with the alphaviral replicase inducing apoptosis in targeted cells which in turn is taken up by dendritic cells, favoring antigen spreading and stimulating cross-presentation for adaptive immunity. 29,30 The potent anti-tumor effect of DREP is likely also attributable to enhanced in vivo delivery using EP previously shown to be superior above others in the case of HPV vaccination. 31,32 Intradermal administration of DREP-E6,7 with in vivo EP significantly increased E7-specific T cell frequencies above that of pVAX.…”

Induction of apoptosis in BCL‐2‐expressing rat prostate cancer cells using the Semliki Forest virus vector

“…Thus p53-independent apoptosis, which is an inherent property of the SFV vector, 10,32 is augmented by expression of the Bax gene from the multicloning site. A consequence of this rapid induction of apoptosis induced by Bax, however, is a reduction in the yield of infectious recombinant SFV-Bax particles using the standard dual helper preparation procedure; 30 this effect may be partially alleviated by low temperature particle production.…”

Replication-defective recombinant Semliki Forest virus encoding GM-CSF as a vector system for rapid and facile generation of autologous human tumor cell vaccines

“…39 Recently, the application of alphavirus replicons has been extended to naked nucleic acids. 40 The relatively high efficacy of self-replicating nucleic acids as compared with DNA vaccines applied in anticancer therapies was correlated with the apoptosis-inducing features of the RNA replicase [41][42][43] and was attributed to mimicking of a viral infection that may trigger danger signals. 44 In contrast to SFV particles, injected nucleic acids are distributed more easily through the body of experimental animals and persist much longer.…”