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Microbes & Immunity Genetic therapy with HSV-1 vectors

HSV-1 monoclonal antibodies and HSV-1-specific nucleic infecting almost all cell lines; (2) it infects both replicating
acid probes. and non-replicating cells, such as neural cells; (3) it can
integrate long exogenous DNA; (4) it is regulated by
3.2. Rapid diagnosis antiviral drugs, such as ACV or gancyclovir (GCV); (5)

After the tissue cells of the oral cavity, cervical mucosa, it is stably present as appendages in neural cells and can
skin, cornea, etc. are smeared, viral antigens are detected continuously express exogenous genes; and (6) mice,
through immunohistochemical staining or indirect pigs, and monkeys can be selected as model animals for
immunofluorescence with specific antibodies. Wright‒ research.
Giemsa staining microscopy revealed that HSV-1 infection With the development of many new technologies,
could be considered if intranuclear inclusions and scientists have used various means to engineer the
multinucleated giant cells were found; negative staining of HSV-1 genome so that exogenous genes can be effectively
herpes blister fluid by electron microscopy could rapidly transmitted and appropriately expressed, greatly reducing
confirm the diagnosis.
harm to the body. Notably, British scientists have been
In situ, nucleic acid hybridization and polymerase working on the use of herpes virus vectors to treat cancer
chain reaction (PCR) can be used to detect viral DNA. for many years and have made remarkable achievements in
Southern blotting was used to determine the specificity of recent years. They successfully treated head and neck cancer
the PCR products, and PCR amplification of cerebrospinal and reported that the use of a combination of radiotherapy
fluid was considered the best means of diagnosing herpetic and chemotherapy to treat cancer is significantly better
encephalitis. In addition, DNA digestion patterns can also than the use of monotherapy. 28
be used for HSV-1 identification and type analysis.
There are three main classes of derivative vectors
HSV-1 antibody determination is of little significance for HSV-1, as shown in Figure 2: (1) amplicon vectors
for clinical diagnosis and is only used for epidemiological (amplicon vectors), (2) replication-deficient vectors
investigation and diagnosis, and the commonly used (defective recombinant vectors), and (3) recombinant
method is enzyme-linked immunosorbent assay. attenuated vectors. 29

3.3. Prevention principle 4.1. Amplicon vector
Avoiding contact with patients or administering specific Amplicon vectors are defective vectors that require helper
antibodies to susceptible people can reduce the risk of plasmids and have relatively high amplification titers that
HSV-1 transmission. Conventional antiviral drugs act can effectively infect neuronal cells. In terms of structure
directly against viral DNA polymerase, so it is difficult to and immunology, the amplicon vector used is the same
remove latent viruses. Acyclovir (ACV), valacyclovir, and as that used for wild-type HSV-1, but it carries multi-
famciclovir can inhibit HSV-1 reactivation after infection. conjoined plasmid DNA rather than the viral genome.
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Several HSV-1 vaccines (inactivated virus vaccines, subunit Amplicons are bacterial plasmids that contain the DNA
vaccines, live attenuated vaccines, live vector vaccines, replication initiation sequence (ori) and DNA cleavage/
DNA vaccines, etc.) are in different stages of development. packaging signal (pac) of HSV-1 in addition to the
4. HSV-1-derived vectors prokaryotic replicons essential for replication in bacteria
and resistance marker genes available for screening but
The genome sequence of HSV-1 is fully understood, and the do not contain any other virus-encoded proteins and
molecular mechanism of viral replication is relatively clear, cannot replicate independently. With the help of helper
with viral DNA containing at least 37 essential genes. The viruses, the circularized amplicon allows efficient DNA
Us region has only one essential gene, gD, so that it can be amplification, encapsulates linear DNA as long as 152 kb
replaced by foreign genes, and the modified genome can into HSV-1 particles (Figure 3), 31,32 becomes an infectious
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carry 4 – 50 kb of foreign genes. It was thus developed as a pseudovirus containing multicopy tandem plasmids, and
carrier for the treatment of certain diseases in humans. 19-21 ensures that the vector replicates extrachromosomal in
These include: (1) transmission and expression of some infected cells, that is, in the form of episomes, and does not
human genes in neural cells 22,23 ; (2) selective destruction cause insertional mutagenesis or positional effects on host
of tumor cells 24,25 ; (3) prevention and immunotherapy cell chromosomes. The HSV-1 tsk strain is a good helper
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against tumors ; and (4) prevention of HSV and other HSV-1 virus whose replication is temperature-regulated
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viral diseases. 27 and can multiply at 31°C while helping amplicon vectors
Compared with other viral vectors, HSV-1 as a vector replicate and package. When the harvested virions were
has the following advantages: (1) it has a wide host range, subsequently cultured at 37°C, the proliferation of HSV-1

Volume 2 Issue 2 (2025) 21 doi: 10.36922/mi.7947