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Microbes & Immunity Genetic therapy with HSV-1 vectors

The timing of HSV-1 transcription and translation are through membrane fusion can complete the replication
tightly regulated. The viral genome encodes more than 80 cycle and initiate infectious proliferation. After the virus
viral proteins throughout the entire cycle. Proteins can enters the cell, the nucleocapsid is delivered to the nuclear
be divided into three phases based on their expression pore, and the viral DNA is released into the nucleus with
kinetics during the viral replication cycle: immediate early the assistance of a variety of viral proteins.
(IE, α), early (E, β), and late (L, γ) phases. Viral replication, Under the control of RNA polymerase II and viral
transcription, and nucleocapsid production all occur in the proteins in infected cells, HSV-1 genes begin to be
host cell nucleus. After viral DNA is released and enters the transcribed and translated, and proteins are synthesized
host cell nucleus, the genome is circularized, and the cortical according to the strict rules of IE gene transcription
protein VP16 interacts with host-related factors and then and expression → production of the IE gene product →
binds to the enhancers of the five IEs (ICP4, ICP27, ICP0, activation and regulation of E gene transcription and
ICP22, and ICP47) of the viral genome (TAATGARAT), expression → production of the E gene product → activation
thus initiating transcription. The expression products
5,6
of IE genes directly affect the transcription of the E gene. and regulation of the transcription and expression of the L
The E gene encodes mainly enzymes and DNA replication- gene → generation of the L gene product in this order. The
synthesis of most viral proteins requires post-processing
related proteins. The last is the expression of gene L, which modifications for their biological functions, including
mainly encodes structural proteins required by some viral phosphorylation, glycosylation, ADP ribosylation, and
particles.
nucleotidylation. The synthesis of viral DNA occurs in the
HSV proteins include viral structural proteins and non- nucleus and requires the participation of many enzymes.
structural proteins. The former includes glycoproteins and Viruses have two main replication modes: theta replication
capsid proteins, and the latter includes enzymes encoded and delta replication. The combination of these two
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by viral genes, such as DNA polymerase, thymokinase, replication modes makes full use of the characteristics of
and DNA replicase-helicase. There are other coat proteins the viral genetic structure to enable it to make full use of
located between the envelope and the capsid. In addition to the host’s limited space and time resources to replicate the
proteins, viral particles also contain spermidine, spermine, progeny viruses as efficiently as possible.
and a small amount of proteins and lipids from host cells.
The assembly of the HSV nucleocapsid occurs in the
Viral genes can also be divided into essential genes and nucleus through three processes: capsid formation, DNA
non-essential genes based on whether they are essential for processing and capsid packaging. The assembled virus
viral growth. These essential genes are essential for viral must first escape from the nucleus to the cytoplasm. In
replication in cultured cells and account for approximately this process, it buds through the nuclear membrane and
half of the viral genes, including capsid proteins, viral undergoes the first outer membrane wrapping process.
DNA replication proteins, viral DNA cleavage/packaging After reaching the cytoplasm, the outer membrane formed
proteins and some cortical proteins. Non-essential genes by the first encapsulation must be removed, and the
are not completely required for viral replication in cultured process of tegumentation must be completed so that a layer
cells, but some non-essential genes may also be essential of tegument is formed on the outside of the nucleocapsid.
for viral growth based on different hosts, pathogeneses and The virus then crosses the plasma membrane again and
latent states. escapes from the cell through a second outer membrane

2.1. HSV-1 replication wrapping process to form the final mature viral particle.
This complete process involves the activities of a variety of
The propagation process of HSV mainly includes viral organelles and a series of biological functions in the cell. 9
adsorption, membrane fusion, invasion, capsid, protein
synthesis, DNA replication, nucleocapsid assembly, 2.2. HSV-1 infection and resistance to environmental
envelope formation, and mature release of virions. 7 and physicochemical factors
The binding of some glycoproteins on the viral surface Humans are the only natural hosts of HSV-1. The virus
to host cell receptors is called adsorption. HSV-1 infects enters the body through the respiratory tract, oral
two main types of cells: epithelial cells and neurons. Some cavity, and damaged skin and is latent in the sensory
specific envelope glycoproteins can recognize host cell- ganglion cells, with most cases being asymptomatic.
surface receptors to achieve specific adsorption. After When the body’s resistance, such as fever, focal infection,
HSV-1 is adsorbed on host cells, it soon enters the cells gastrointestinal dysfunction, and emotional changes,
through membrane fusion, which is the fusion of the viral decreases, latent HSV-1 in the body is activated to cause
capsule and the cell membrane. HSVs that enter cells related diseases. When HSV-1 infects healthy people,

Volume 2 Issue 2 (2025) 18 doi: 10.36922/mi.7947