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Microbes & Immunity Genetic therapy with HSV-1 vectors

disease through reactivation. However, the latent infection 2. Biological characteristics of HSV-1
of viruses and the precise molecular mechanisms involved
in the progression from latent infection to reactivation HSV is a typical representative of Herpesviridae and
are still unclear, and this mechanism may differ among has two serotypes, HSV-1 and HSV-2. The HSV-1 viral
particles were spherical with a diameter of 100 nm. As
different viruses.
shown in Figure 1A, the double-stranded DNA genome
Latent infection is different from chronic infection and viral DNA-binding proteins together constitute the
in that there are no infectious progeny. Conversely, viral core, which has a diameter of approximately 75 nm.
this reactivation ability differentiates latent infection The capsid protein is wrapped around the core, and
from abortive infection. Latently infected viruses can 162 capsomeres form an icosahedral three-dimensional
simultaneously be latent in some cells and actively symmetric structure. The core and capsomere form
multiply in other cells. Therefore, there are several different the capsid. On the outside of the nucleocapsid is an
situations: (1) the virus is essentially latent in all cells (this asymmetric and homogeneous tegument that tightly
seems to be the case for VZV; the possibility is low for HSV); surrounds the capsid. The cortex contains at least 20
(2) in some of the infected cells, the virus undergoes lytic viral proteins, some of which are very important for the
activation, but there are no associated symptoms (such as transcription initiation of viral DNA and the replication
asymptomatic virus shedding in HSV, which is a common of viral particles. The cortex is an envelope that contains
phenomenon for all herpesviruses, including VZV); and various lipoproteins and has various protrusion
(3) lytic replication or proliferation of the virus, which is structures; they are glycoproteins encoded by the virus.
the essential cause of the disease (some cells remain in the At present, 13 different viral glycoproteins have been
4
latent state). found to be involved. Once the membrane of the viral
particle is removed, it enters the host cytoplasm and
HSV-1, the first human herpesvirus discovered, has reaches the nuclear membrane along tubulin, after which
been intensively studied. Its biological properties are the viral DNA is injected into the nucleus through the
attractive, especially the following characteristics: (1) it nuclear pore.
can cause a series of infections; (2) it can cause a lifelong
latent infection in the host; and (3) reactivation can cause The HSV genome is a double-stranded linear DNA
damage at or near the initial infection. Herpesviruses can sequence with a length of approximately 152 kb. The
be used as research models and research tools to investigate HSV genome is replicated in a rolling circle in the host
intercellular protein shuttling, synaptic connections in the cell to form an end-end concatemer DNA. As shown
in Figure 1B, the genome is mainly composed of two
nervous system, membrane structure, gene regulation, covalently linked fragments, that is, a long fragment (UL)
gene therapy, cancer treatment and many other biological and a short fragment (US). These regions are flanked by
problems (including the general biological characteristics the short inverted repeat sequences TR -IR and IR -TR
S
of other viruses and the specific biological characteristics respectively. In addition, at the two ends of the double- S,
L
L
of HSV). stranded DNA and the junction of there is a single
IRL-IR S,
Since the release of the HSV-1 genome sequence copy of “a,” which contains the packaging and entry signals
in 1988, many scientific researchers have focused on of viral DNA.
1
the effects of the HSV-1 gene on viral replication and
pathogenicity. After more than 20 years of hard work, many A
genes involved in the regulation of viral gene expression,
host protein interactions, and evasion of host immunity
have been identified.
As an important viral family that infects humans, HSV-1
can infect all human tissues and establish latent infection
in the host. HSV-1 is a complex neurotropic virus that
2,3
can be transmitted antegrade or retrograde through
the synapses of neurons and can establish a stable latent
infection in neurons without affecting their function. To B
date, HSV-1 vectors have been developed into viral vectors
that effectively introduce exogenous genes into the nervous
system and are gradually being applied for the treatment of Figure 1. Schematic diagram of the herpes simplex virus (HSV) (A)
various diseases, including tumors. structure and (B) DNA structure

Volume 2 Issue 2 (2025) 17 doi: 10.36922/mi.7947