| Varicella-zoster
virus (VZV) is a member of the herpes virus group,
(alpha) herpes virus 3. It is a DNA virus
Primary VZV often causes the disease known as
chickenpox. Chickenpox can be severe and have
a number of complications. After a primary infection,
the virus enters the sensory nerves and becomes
latent in the dorsal root ganglia along with spinal
column. Decades later the virus may reactivate
and moves down the same nerve, to cause the disease
known as shingles. Thus, shingles is the same
virus that was first acquired 20-40 year earlier.
Prior to 1998, the dogma among virologists was
that VZV had only minimal diversity around the
world. In other words, VZV was the same virus
in the United States, the United Kingdom, India,
Thailand or Japan. Similarly, VZV was considered
to be the same serotype around the world also.
In 1998, the first
report was published, which described
the discovery of a community VZV strain with a
mutation in one of the major surface glycoproteins
called gE. The strain was designated VZV-MSP,
because it was discovered in the Minneapolis-St.
Paul metropolitan area of Minnesota. What is most
unusual about this mutant strain is that it has
a phenotype that is distinguishable from most
other community VZV strains. The altered phenotype
relates to patterns of egress. Most community
VZV strains emerge from infected cells in a pattern
called “viral highways,” long rows
of virions across the surface of an infected cell.
In contrast, the mutant virus strain VZV-MSP emerges
in a uniform pattern over the surface of the infected
cell.
The mutant virus has also been tested in the
severe combined immunodeficient (SCID-hu) mouse
model. In this model, human skin explants are
inserted under the skin of the SCID mouse. VZV
is then infected into the human skin and subsequently
examined after pathological sectioning and staining.
When typical community strains were compared with
VZV-MSP in the SCID-hu model, it was observed
that the mutant virus spread faster. In another
assay of cell spread, VZV-MSP spread about 30%
faster than most other community strains. Although
the SCID-hu model does not measure virulence,
the attribute of increased cell spread is compatible
with increased virulence.
When VZV-MSP was originally discovered and reported,
it was considered by many virologists to be an
extraordinarily rare event, perhaps never happening
again. However, just four years later, another
gE glycoprotein mutant virus was
discovered in a 70 year old Canadian man, who
had a severe case of shingles on the face. The
fact that two gE mutant viruses have been discovered
within a few years of one another leads to a startling
conclusion. Populations of mutant gE viruses may
exist in circumscribed geographic areas in the
US and Canada.
In summary, VZV is not the same genotype or the
same phenotype around the world. Genetic diversity
and phenotypic diversity certainly exist. In future
years, by collecting VZV samples from around the
world, we will be able to determine the extent
of this diversity.
The following web sites contain detailed information
regarding Varicella-zoster virus:
CDC
varicella web page
Dr.
Charles Grose's varicella laboratory web site
National Immunization Program Information on Varicella Vaccine
US
states requiring varicella vaccine administration
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