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Microbes & Immunity Genetic therapy with HSV-1 vectors

they can rapidly develop immunity, and the lesions are and damaged skin. Serological surveys have shown that
limited to only the skin and mucous membrane surfaces. the level of HSV-1 antibody is directly related to age and
Severe HSV-1 reactivation is often induced in people socioeconomic status. In most underdeveloped countries,
with deficient immunity (organ transplantation, patients 90% of people over 30 years of age are positive for HSV-1.
receiving immunosuppressants and antitumor therapy) Approximately 50 – 60% of the middle-class population
and those with immature immune function. After in the United States has detectable levels of antibodies to
neonates are infected with HSV-1, lesions, such as those HSV-1, while that of the group with poor socioeconomic
in the brain, liver, eyes, adrenal glands, lungs, and skin and status is close to 90%. After the first infection in healthy
mucous membranes, often spread throughout the whole humans, patients usually have no clinical symptoms and
body, resulting in severe conditions and high mortality. then develop a latent infection. HSV-1 causes mainly
When extensive skin injury occurs, such as eczema and pharyngitis, cold sores, and keratoconjunctivitis.
burns, HSV-1 often manifests as generalized herpes on
the skin and mucous membranes and can be transmitted 2.4. HSV-1 infection
throughout the body to cause disease. HSV-1 relies on the binding of glycoproteins on the
envelope to host cell-surface receptors so that the envelope
HSV-1 can adapt to a wide range of host cells and
can reproduce in various passages of cells with obvious fuses with the cell membrane of infected cells, the cortex
and capsid then enter the cytoplasm, and the capsid docks
cytopathy. HSV-1 has a wide host range; except in in the nucleoporin complex. The viral DNA is injected into
humans, it can infect almost all kinds of epithelial cells
and fibroblasts from embryos and neonatal animals. The the nucleus with the help of nucleoporin, and then, the
replication cycle of HSV-1 is 12 – 18 h in most sensitive cell replication of new viral DNA and transcription of mRNA is
lines, and cytopathic cells appear 24 – 48 h after infection. performed in the nucleus. The new virus buds through the
nucleolus to form an envelope and then buds via similar
HSV-1 is sensitive to heat and dryness and can be protein transport to become a mature progeny virus.
inactivated in a 50% humid heat environment or a 90%
dry environment for 30 min. The median lethal period 2.4.1. Acute infection
of ultraviolet (UV) light is 5 – 7 s, and 2 min of X-ray In HSV-1-infected cells, virus-specific gene products are
exposure at 1200 rad can inactivate 90% of the virus. The tightly chronologically regulated. IE proteins synthesized
viruses were inactivated after treatment with 1% phenol 2 – 4 h after infection may play a regulatory role in viral
(phenol, phenolic acid) for 3 days at room temperature and transcript levels. The synthesis of the E protein inhibits the
then treated with 5% phenol at 4°C for 18 h. Treatment synthesis of the IE protein while it induces the synthesis
with ethanol, ether, or chloroform at 4°C for 18 h can of the L protein. Late proteins are generally synthesized 12
inactivate HSV-1 in the liquid but has little effect on the – 15 h after viral infection of cells and are components of
virus in a dry environment. The viruses were inactivated viral particles. The local infiltrating cells of viral infection
by treatment with 1:1000 potassium permanganate for 1 h are initially neutrophils, followed by mononuclear cell
at room temperature. At 35°C, 0.01 mol/L formaldehyde or infiltration.
virus at 100 – 1000 pfu/mL (pfu: plaque forming unit) can HSV-1 is able to spread through the central ganglia or
be completely inactivated by treatment with 0.001 mol/L networks of cells innervated by axon nerves and lurks in
iodine for 1 h.
the sensory and autonomic ganglia.
HSV-1 is stable in solution with protein, so 10% horse
serum or rabbit serum, 0.1% egg yolk or 0.5% gelatin are 2.4.2. Latent versus active infections
commonly used to preserve the virus. When cysteine is The virus enters the cell bodies of sensitive ganglia
present in a viral suspension, it can prevent the oxidation from peripheral ganglia through axonal transport and
of the virus and protect the virus. Virus-infected tissues then undergoes lytic or latent infection. HSV-1 was
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can be stored in 50% glycerol at 4 – 8°C for half a year. The demonstrated to be latent in the trigeminal ganglion,
HSV can be stored for several years after lyophilization. superior cervical ganglion, and vagus ganglion and
occasionally in the dorsal sensory nerve roots of S2-3, as
2.3. Pathogenicity and immunity of HSV-1
demonstrated by coculture. In the latent infected state, the
HSV-1 infection is very common and has a global genome of the virus is encapsulated by histones but does
distribution. Humans are the only natural hosts of HSV-1, not integrate into the host genome. In this state, the virus
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which is transmitted mainly through direct and close enters a relatively quiescent state; almost none of the viral
contact. Viruses can invade the body through various genes are transcribed, and only some viral RNAs associated
channels, including through the mouth, respiratory tract, with latency (LAT and miRNA) are still transcribed.

Volume 2 Issue 2 (2025) 19 doi: 10.36922/mi.7947