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Introduction to Herpes Simplex Virus

Herpes simplex virus-1 (HSV-1) is an enveloped, double-stranded DNA virus with several advantages for use as an oncolytic virus: a large genome suitable for insertion of foreign genes; tropism for neural cells; a safety mechanism in its sensitivity to agents, such as ganciclovir; high titers can be generated; and it does not integrate into the host genome, so it is unlikely to be oncogenic. These advantages have led to the use of HSV-1 genetically engineered to be replication-conditional, i.e., selectively dividing in replicating cells, as oncolytic viruses in the treatment of numerous cancer types.

 

Herpes simplex virus-1 (HSV-1) particle is made up of four layers. The viral genome is a 153-kb double-stranded DNA molecule, enclosed in an icosahedral capsid that is surrounded by the tegument, a rather unstructured layer containing some 20 virus-encoded proteins. The tegument is delimited by the envelope , which is a lipid membrane of cellular origin, containing a dozen virus-encoded glycoproteins.

 

The viral genome is arranged as two unique sequences-Unique Long (UL) and Unique Short (US)-that are each flanked by repeat sequences. Homologous recombination at these repeat sequences results in four possible permutations of linear and inverted UL and US sequences. During infection and after cell entry mediated by surface glycoproteins, the viral genome circularizes and begins transcription of immediate early (IE) genes, which are involved with transcription regulation of the host cell and virus. The IE genes also contribute to transcription regulation of early (E) and late (L) genes.

 

Reference:

Agarwalla P.K., Aghi M.K. (2012) Oncolytic Herpes Simplex Virus Engineering and Preparation. In: Kirn D., Liu TC., Thorne S. (eds) Oncolytic Viruses. Methods in Molecular Biology (Methods and Protocols), vol 797. Humana Press

Marconi P., Fraefel C., Epstein A.L. (2015) Herpes Simplex Virus Type 1 (HSV-1)-Derived Recombinant Vectors for Gene Transfer and Gene Therapy. In: Lossi L., Merighi A. (eds) Neuronal Cell Death. Methods in Molecular Biology (Methods and Protocols), vol 1254. Humana Press, New York, NY