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Microbes & Immunity Correlation between VZV and cancer

less common but significant complications associated complications. Regardless of immune status, VZV
with HZ, such as HZ ophthalmicus, disseminated zoster, establishes lifelong latency in sensory ganglia through
meningitis, encephalitis, cranial nerve palsies, and retrograde axonal transport and potentially through
more. However, one complication that has yet to reach a hematogenous spread. Hematogenous dissemination
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consensus is the development of cancer secondary to HZ may lead to less common but serious infections associated
infection. with VZV. Complications include VZV encephalitis,
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cerebellar ataxia, demyelinating neuropathy, myelitis,
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3. VZV’s effects on the immune system pneumonia, meningitis, and vasculopathy. 39
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The reactivation of latent VZV in the dorsal root ganglia Foreign DNA detection is necessary to amount an
remains poorly understood. Immunodeficient states innate immune response during VZV infection. VZV can
caused by coinfections, medications, or other diseases evade DNA sensing through antagonism of the cytosolic
strongly correlate with reactivation. Age is another key DNA sensor cyclic GMP-AMP synthase (cGAS) using
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factor, with 68% of HZ cases occurring in individuals VZV tegument protein ORF9. The cGAS pathway
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over 50. Further clarification is needed to determine if ultimately leads to the production of type I IFN; however,
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HZ effects on the immune system make the body prone inhibition of this pathway allows for viral persistence
to cancer manifestation or if cancer diagnosis after HZ and chronic inflammation, which are known risk factors
infection is a result of undetected cancer-suppressing for oncogenesis. Inhibition of the cGAS is especially
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the immune system allowing for VZV reactivation. In important in this discussion as interruption of this
addition, understanding how VZV manipulates the pathway has been shown to have significant implications
immune system to establish latency could provide insights in cancer biology. In a normal physiological state, cGAS
into its reactivation mechanisms and potential oncogenic interferes with homologous recombination-mediated
properties. 3 DNA repair, thus promoting tumor growth. In addition,
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After exposure to infected respiratory droplets, VZV cGAS localization in the mitochondria helps maintain
initially infects epithelial cells and resident dendritic mitochondrial function, reduces reactive oxygen species
cells in the upper respiratory tract. It then reaches local accumulation, and prevents ferroptosis which facilitates
lymphoid tissues and transfers to mature T-lymphocytes. tumor growth. Alternatively, tumorigenesis may be
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Early theories suggested VZV preferentially infected promoted by a decrease in type I IFN, as discussed later
T cells with specific phenotypes, but newer evidence in this review, making cancer manifestation through cGAS
indicates that VZV activates T cell signaling and remodels modulation a multifaceted subject.
surface proteins, impairing immune function. RNA Controlled process of programmed cell death that helps
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sequencing of T cells from the lungs of simian varicella maintain the balance of cell life and death in the body with
virus (SVV)-infected rhesus macaques showed that genes key roles in the elimination of damaged or abnormal cells,
involved in gene regulation, cell cycle progression, and removal of infected cells during an immune response,
antiviral immune responses were activated, whereas genes and prevention of autoimmune responses by eliminating
related to antigen presentation and cellular metabolism cells with autophagy potential. The usual viral infection
were suppressed. In addition, VZV disrupts immune immune response is accompanied by induction of
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responses by altering apoptotic signaling, interferon (IFN) programmed cell death. Literature suggests VZV plays a
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signaling, and immune-related genes such as CXCL10 and role in the modulation of apoptotic processes in neuronal
IRF1. 30,31 The infection progresses through dissemination cells through Bcl-2 upregulation. In immune cells, VZV
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into the bloodstream to internal organs before undergoing has been shown to induce apoptosis; however, Steain et al.
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a 2-week incubation period. The infection progresses by observed increased apoptosis in human fetal fibroblasts
disseminating through the bloodstream to internal organs compared to human fetal sensory neurons. This anti-
during a 2-week incubation period. It then moves from apoptotic tropism in neuronal cells has been identified
the respiratory mucosa to the skin, infecting keratinocytes in other studies observing the genes associated with the
and causing vesiculopustular exanthema, which manifests inhibition of apoptosis (Trail-R4, BIRC5 [SURVIVIN],
as highly contagious lesions across the body and mucous and BAG3) in human embryonic stem cell-derived
membranes, including the oral cavity. neurons. It was found that genes protective of apoptosis
In immunocompetent individuals, primary VZV were increased in neuronal cells as opposed to non-
infection is typically self-limiting and resolves within neuronal cells. In addition, non-neuronal cells were found
2 weeks. However, immunocompromised individuals have increased expression of pro-apoptotic genes, such as
may experience more extensive dissemination and caspase-3; proteins, such as Fas-associated death domain,

Volume 2 Issue 3 (2025) 17 doi: 10.36922/mi.8320