Overview: Varicella-zoster virus (VZV)
enveloped, double-stranded linear DNA virus
with an icosahedrally arranged capsid, and a member of the Herpesviridae family, related
Epstein-Barr virus, of the same subfamily
(α-Herpesvirus) as the
herpes simplex viruses
(HSV-1 and HSV-2) (Figure 1).
VZV virions are spherical and roughly 150 nm
(nanometres) to 200 nm in diameter and possess
a genome that is slightly less than 125000 base
pairs in length (Cohen et al., 1998). The capsid is surrounded by a number of
loosely associated proteins collectively known
as the tegument; many of these proteins play
critical roles in initiating the process of
virus reproduction in the infected cell. The
tegument is covered by a lipid envelope studded
with glycoproteins that are displayed on the
exterior of the virion. The known envelope
glycoproteins (gB, gC, gE, gH, gI, gK, gL)
correspond with those in HSV. VZV commonly causes
in children and both
postherpetic neuralgia in adults.
Electron micrograph of a varicella virus.
Life Cycle and
Clinical Infections: The virus is
transmitted in fluids, primarily from coughing
or sneezing (Figure
2). It can also be transmitted by skin
contact or via contaminated air particles.
Once the virus is inhaled, its infects the
conjunctivae or the mucosae of the upper
respiratory tract, and two to four days after
infection, begins to proliferate in the regional
lymph nodes of the upper respiratory tract. This
results in the childhood disease varicella or chickenpox.
Chickenpox is a highly contagious acute
infection, which results in mild fevers,
itching, fatigue, skin lesions, and blister-like
rashes covering the whole body, but usually more
concentrated on the face, scalp, and trunk
(Figure 3). While the disease is usually mild, a
very small proportion of children (1 in every
develop VZV encephalitis – an
acute, severe, neurological disease (Cohen
et al., 1998).
Transmission electron micrograph of
varicella-zoster virions from vesicle fluid of
patient with chickenpox.
This photograph depicts the left shoulder
region of a bedridden elderly male who was at
first glance, thought to be suffering with a
case of smallpox,
which was subsequently determined to be a case
Viremia, or infection of the
bloodstream, soon follows. About 14 to 16 days
after infection, secondary viremia causes a
second round of replication, this time mainly in
the body's internal organs (mostly liver and
spleen). This secondary viremia also is
characterized by viral invasion of capillary
endothelial cells and the epidermis, resulting
in the characteristic vesicles of chickenpox.
After primary infection of VZV, the virus
spreads from mucosal and epidermal cells to
nerve cells, especially the dorsal root ganglia,
where it remains latent until reactivation later
in life. The pathogen usually
reactivates as a result
of severe stress or immunosuppression, resulting in herpes zoster (more commonly known as
shingles), a condition characterized by pain and renewed lesions.
Despite a low rate of occurrence, herpes zoster
infections are a major health and economic
concern in some locations; Cheong et al.
(2010) reported an annual cost of over $75
million in Korea, highlighting the economic, as
well as health benefits of widespread
Zoster sine herpete is
an infection associated with viral reactivation, causing patients to exhibit
pain and motor weakness, but no visible skin
lesions. In as many as 25% of shingles cases
reported, acute facial paralysis may result. The
pain in the areas affected by shingles is
referred to as postherpetic neuralgia; this pain may become a
chronic issue, persisting years after the
infection has otherwise healed (Cohen
et al., 1998). The risk of postherpetic neuralgia increases with age, and in
extremely rare cases, the infection can lead to
hearing problems, blindness, and death (Cheong
et al., 2010).
When VZV particle first encounters a
targeted cell, it docks with cell surface
proteins, in particular mannose 6-phosphate
receptors. The viral envelope then fuses with
the plasma membrane of the cell and the viral
capsid containing the viral genome and tegument
proteins enter the cytoplasm. The capsid then
travels along a microtubule towards the nucleus
where it docks with a nuclear pore. The viral
DNA enters the nucleus through the pore and
before replication. New viral capsids assemble
in the nucleus and daughter genomes are taken
into them. The capsids bud through the inner
nuclear envelope gaining a temporary envelope
that surrounds them during their stay in the
perinuclear space. This envelope then fuses with
the outer nuclear envelope and the now naked
capsids progress through the cytoplasm until
they bud into Golgi vesicles laden with viral
proteins. This budding into the vesicle
furnishes the developing virion with tegument
proteins, an envelope and surface projections.
The vesicle delivers the contained virion to the
cell surface. The vesicle fuses with the plasma
membrane and the new virus particle is free to
infect another cell.
Identification: The infection is often readily
identifiable due to characteristic rashes
produced, but Tzanck smearing or culturing fluid
from a vesicle can confirm the diagnosis. Early
diagnosis of Zoster sine herpete can be
enzyme-linked immunosorbent assay (ELISA) testing.
VZV is readily preventable by
vaccination, with 80% to 90% of immunized subjects
exhibiting total immunity to chickenpox (Cheong
et al., 2010). In fact, since the
vaccine's introduction, there has been a
significant decline in varicella-related deaths
and hospitalizations. Vaccinated individuals who
do suffer an infection usually experience mild
can be treated by a number of drugs and
therapeutic agents including acyclovir for the
chickenpox, and famciclovir and valaciclovir for
the shingles. Immune response can also be
boosted by administering varicella zoster immune
globulin or VZIG, but it is only administered when there is a risk of severe complications
occurring. The virus is also susceptible to
disinfectants, notably sodium hypochlorite.
Choi, W.S., Huh, J.Y., Jo, Y.M., Kim, W.J., Lee,
J., Noh, J.Y., & Song, J.Y. (2010). In Press.
Disease burden of herpes zoster in Korea.
Journal of Clinical Virology, 47(7):
Cohen, J. I.,
Cox, E. Iofin, I., Reddy, S.M., & Soong, W.
(1998). Varicella-Zoster Virus ORF32 Encodes a
Phosphoprotein That Is Posttranslationally
Modified by the VZV ORF47 Protein Kinase.
Journal of Virology, 72: