Herpes Simplex Virus 1 (HSV-1)-Based Vectors - Viral Vector Approaches in Neurobiology and Brain Diseases - page 50

Glycoprotein spikes

Envelope

Outer tegument

Inner tegument

Capsid

DNA

Fig. 1 Schematic representation of the HSV-1 particle. The viral particle is made
of a double-stranded linear 153-kbp core DNA, a capsid composed of 162 cap-
somers, a lipid envelope in which are embedded viral proteins and glycoproteins
(glycoprotein spikes), and the relatively amorphous layer of tegument proteins
(sometimes divided in inner and outer tegument proteins), located between the
capsid and the envelope

and S (short). Each element consists in unique sequences (UL and
US) bracketed by inverted repeats. The repeats surrounding the L
component are designated TRL (terminal repeat L) and IRL (inter-
nal repeat L) or ab and b , whereas those surrounding the S com-

ponent are designated IRS (internal repeat S) and TRS (terminal
repeat S), or a

′ a ′

and ca . The number of a sequence repeats at the
L/S junction and at the L terminus of the DNA molecule is vari-
able, but generally there are more than one a repeat, whereas at the
S terminus there is only one a sequence. The structure of the virus
genome and its replication cycle is represented in Fig. 2 . Although
linear within the particle, the virus genome circularizes immediately
after infection. Even though the exact mechanism has not been
established yet, the circular genome is replicated using a combination
of homologous recombination and rolling circle amplifi cation [ 3 ].
The UL component of the virus genome contains at least 56
unique genes (UL1 to UL56), whereas the US component contains
at least 12 unique genes (US1 to US12). The inverted repeats fl ank-
ing UL ( b and b

′ c ′

sequences) express 3 genes: a fi rst encoding the
immediate early regulatory protein ICP0 (infected cell polypeptide
0), a second encoding the late neurovirulence protein ICP34.5,
and a third encoding a family of transcripts globally known as latency-
associated transcripts (LATs). The LATs, which encode no proteins,
are expressed antisense respective to the genes encoding IPC0 and
ICP34.5. The inverted repeats fl anking US ( c and c

′

sequences)
express a single gene, encoding the immediate early regulatory pro-
tein ICP4. The a sequences contain no transacting genes. Therefore,
the HSV-1 genome contains at least 76 canonical genes of which 4
(encoding ICP0, ICP4, ICP34.5, and the LATs) are duplicated

′