Page 29 - MI-2-3

Microbes & Immunity Correlation between VZV and cancer

correlations for VZV reactivation have been observed, such from embryonic rats demonstrated that latent HSV-1 was
as immunosuppression due to age, medication, concurrent reactivated in response to NGF deprivation. The study by
86
infection, and disease, the specific mechanistic cause has Thellman et al. utilized an immortalized human dorsal
87
yet to be determined. A notable factor is decreased T-cell root ganglion cell line (HD10.6) to model HSV-1 latency
immunity, particularly in aging individuals or those and reactivation. They found that HSV-1 infection in these
undergoing immune-suppressive treatments, which can human neurons resulted in a quiescent state resembling
trigger VZV reactivation and lead to HZ. This suggests that latency, and reactivation could be induced by depletion
CD4 and CD8 T cells play a critical role in maintaining of NGF, indicating that NGF is crucial for maintaining
+
+
VZV latency and preventing reactivation. 80 latency in human neurons as well. Furthermore, Cohrs
et al. found that interruption of NGF signaling in human
88
Evidence for this postulation comes from research
by Arnold and Messaoudi on primate models studied, trigeminal ganglia led to an increase in VZV DNA, although
29
89
where animals with higher viral loads in their nerve full viral replication was not noted. Sadaoka et al. further
clusters (ganglia) were more likely to experience mild, demonstrated that treatment of latently infected human
neurons with antibodies to NGF resulted in the production
asymptomatic reactivation compared to those with of infectious VZV in about 25% of the cultures, indicating
lower viral levels. Subclinical reactivation was associated that NGF deprivation can trigger reactivation. HSV, in the
with higher viral levels in the ganglia. In SVV-infected same Herpesviridae family as VZV, on the other hand, is
29
BSC-1 cells, significant reductions in key proteins such 90
as STAT1, JAK1, and JAK2 were observed. In addition, able to reactivate fully in vitro in cadaver ganglia. These
findings highlight the importance of NGF in maintaining
the activation and nuclear movement of STAT1 were VZV latency and suggest that its interruption can lead to
blocked, though this was not due to cellular or viral viral reactivation, although additional factors or conditions
enzymes. Furthermore, VZV reactivation has been are likely required for complete viral replication and
81
linked to co-infections, such as mycobacterial infections reactivation. 89
and reactivated herpes simplex virus 1 (HSV-1). However,
it remains uncertain whether specific antigens are directly 4.2. PI3-Kinase/Akt pathway in VZV latency and
associated with VZV reactivation or these occurrences reactivation
simply reflect a weakened immune response. 82
The PI3-kinase/Akt pathway is involved in regulating
Investigations into the severity of disease progression several cellular functions, including cell survival, growth,
following reactivation and viral load provided valuable and metabolism, which are essential for maintaining viral
insight into anticipation of VZV pathogenesis. Real-time latency and facilitating reactivation. Studies have shown
quantitative polymerase chain reaction (qPCR) is used that the PI3-kinase/Akt pathway is activated during VZV
83
to quantify the genome copies of pathogens in samples. infection and is necessary for efficient viral replication.
Using qPCR, it was found that in patients with PHN, Inhibition of this pathway can lead to a decline in viral
higher viral loads persisting over time are linked to a replication and an increase in apoptosis. Specifically, the
91
longer recovery period. Viral loads measured in patients VZV ORF12 protein activates the PI3K/Akt pathway to
with neurologic symptoms; however, showed significantly regulate cell cycle progression, which is crucial for viral
lower viral loads compared to patients with HZ without replication in both dividing and non-dividing cells. In
92
neurological symptoms. In addition, less than half of the human stem cell-derived neurons, VZV can establish a
patients experiencing neurological symptoms in one persistent non-productive infection that can be reactivated
study had detectable serum levels of VZV DNA. Viral by inhibiting the PI3-kinase pathway. This suggests that
84
93
load detection may be valuable in patient prognosis; the PI3-kinase/Akt pathway is involved in maintaining
unfortunately, there are limited studies investigating viral latency and that its disruption can trigger reactivation.
load and cancer manifestation.
4.3. c-Jun N-terminal kinase (JNK) pathway in VZV
4.1. Nerve growth factor’s (NGF) effects in VZV latency and reactivation
latency and reactivation
The JNK pathway is a critical component of the mitogen-
NGF is crucial for the survival and maintenance of sensory activated protein kinase (MAPK) signaling pathways. It is
neurons and plays a significant role in the reactivation primarily involved in regulating cellular processes such as
of VZV from latency. Because both HSV and VZV apoptosis, inflammation, and stress responses. Activation
establish latency in neurons, HSV animal models have of the JNK pathway leads to the phosphorylation of c-Jun,
been used to study the intricate mechanism of latency a transcription factor that forms part of the activator
and reactivation. Animal studies on neuronal cultures protein-1 (AP-1) complex, which then transactivates
85

Volume 2 Issue 3 (2025) 21 doi: 10.36922/mi.8320