Semliki Forest Viral Vectors for Gene Transfer
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Semliki Forest virus (SFV), Sindbis virus, and several pathogenic encephalitis-producing viruses (e.g., Ross river virus, RRV) are members of the family Togaviridae and genus Alphavirus. A typical alphavirus is an enveloped virus with single-stranded, positive-polarity RNA genome of approx 12,000 nucleotides. The genome is capped at the 5′ end and polyadenylated at the 3′ terminus. The alphaviral genome functions directly as a messenger RNA, encoding a polycistronic protein that is cleaved into four nonstructural proteins (nsP1-4). These proteins associate with cellular factors and form so-called replicase complexes. These complexes mediate the replication of the plus-strand genome into full-length minus strands, which efficiently produce both new genomic RNAs and a second subgenomic RNA in an autocatalytic manner 1(see Fig. 1 ). Subgenomic RNA encodes the structural proteins that are building blocks for the alphavirus nucleocapsid. Alphavirus gene expression is transient by nature and takes place exclusively in the cytoplasm of the host cells. Replication of alphaviruses is extremely efficient with approximately 105 new virions per cell being produced with the aid of the host’s own translational machinery. For review of alphaviruses, see ref. 1 .
Fig. 1. Schematic presentation of alpha virus replication. The genomic RNA is first used as template for the synthesis of non-structural proteins that form enzyme complex called replicase. This complex can copy the+strand genome into - strand genome and vice versa, using the genomic 42S promoters. Replicase can also utilize the subgenomic 26S promoter and synthesize subgenomic message that encodes the structural proteins of SFV virions.
