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