Polyomaviruses
Polyomaviruses belong to Polyomaviridae family of viruses which
comprises one genus, eleven species, seventeen subspecies, and nineteen
unclassified members. Polyomaviruses are small DNA viruses capable of persistent
infection. Presence in the upper respiratory tract may be a general property of
human polyomaviruses. BKPyV, JCPyV , WUPyV, and KIPyV have also been identified
in fecal specimens, which suggests their potential for transmission through the
gastrointestinal (GI) tract. Two major types of particles are found in cells
infected with these viruses: Virions containing viral DNA and protein,
and empty capsids, or protein shells, that are noninfectious. Host cell
histon proteins associate with viral DNA and form mini-chromosome-like
structure.4,6,10
Polyomaviruses require the apparatus of cell DNA synthesis for their own
replication. To meet this need they have evolved many different ways to
intervene in cell growth regulation. This intervention can cause tumors in
humans and animals. To date, five genetically distinct human polyomaviruses have
been identified.
BK polyomavirus (BKPyV) was first isolated from the urine of a patient
on immunosuppressive therapy following kidney transplantation. BKPyV appears to
be a common infection in humans which usually produces no symptoms. Much of this
host resistance is attributed to the remarkable ability of T-cell immunity to
prevent virus activation. BK polyomavirus has been associated with mild
respiratory disease in children and can be detected in tonsils.1 The
virus also commonly infects the urinary tract.
BK polyomavirus uses several mechanisms to induce tumors. It targets and
inhibits several key cell cycle regulatory genes, including p53, a tumor
suppressor gene. The virus produces a number of T-proteins, or tumor-initiating
proteins. BK polyomavirus also causes structural changes in chromosomes and
damages DNA repair mechanism.
Since its discovery in the early 1970s, BK polyomavirus has been isolated in
a variety of human tumor cells, including prostate cancer, adrenal cancer, renal
cell carcinomas, colorectal cancer, brain cancers, cervical carcinoma, genital
tumors, Kaposi sarcoma, bone cancer, urinary tract tumors, and insulinoma (tumor
of the pancreatic islets).3
JC polyomavirus (JCPyV) is closely related to BKPyV and simian
vacuolating virus 40 (SV40). It was first isolated in 1971 from the brain tissue
of a PML patient. It is estimated that 70-80% of the world population is
infected with this virus early in childhood without apparent clinical symptoms.
JCPyV viral DNA has also been detected in tonsils. The virus establishes a
persistent infection in the kidneys and is reactivated under immunocompromised
conditions.4 JCPyV infects and destroys olygodendrocytes which are
myelin-producing cells in the CNS, and indirectly causes death of neurons in the
white matter of the brain. The destruction of both oligodendrocytes and neurons
results in PML, a neurodegenerative disease. JC polyomavirus has been implicated
in the development of lung cancer, colorectal cancer, esophageal carcinoma, and
brain cancers.3,5
KI polyomavirus (KIPyV) (Karolinska Institutet virus) was first
isolated in 2007 from children less than 5 years of age with respiratory tract
infections who had conditions ranging from a common cold to acute respiratory
distress.. Primary infection with this virus occurs during childhood or
youth.5,9
WU polyomavirus (WUPyV) (Washington University virus) was
initially isolated in 2007 from a patient with acute respiratory tract
infection. The virus has a worldwide distribution and has been detected in
respiratory secretions from patients with respiratory diseases. Primary
infection with this virus occurs during childhood or youth. Young children may
be susceptible to infection with this virus and occasionally the infection with
this virus may cause severe disease. WUPyV has been suggested to be a
respiratory pathogen. The most common clinical findings are cough and
wheezing.
WU polyomavirus has also been detected in specimens from the GI tract.
However, it's precise role in GI disease remains unclear. WUPyV may act as an
opportunistic pathogen in the GI tract, colonize the GI tract without causing
any disease, or be a part of the internal viral flora that are reactivated by
other viral infections. It has been suggested that WU polyomavirus can be shed
for prolong periods following previous acute infection.8,9,11
So far, WUPyV infections can not be distinguished from other viral infections
by means of clinical symptoms. Respiratory tract disease like pneumonia or
bronchitis is frequently observed in patients harboring WUPyV.12
Merkel cell polyomavirus (MCPyV) was discovered in 2008 in Merkel cell
tumor, a rare form of skin cancer. Subsequently, MCPyV has been isolated from
human respiratory secretions which indicates that it is shed into the
respiratory tract or present in cells of the respiratory tract, similar to
KIPyV, WUPyV, BKPyV, and possibly JCPyV. However, conclusions about their
primary target organs and pathogenicity can be drawn based on further
investigation.6
The fact that Merkel cell polyomavirus is found in the malignant cells
provides proof that this virus is directly involved in the cancer initiation
process predicted by previous research with SV40 and murine PyV (MPyV). This
discovery is another reminder that we certainly have not seen the end of new
human polyomavirus identification, but rather the beginning of a new
era.7
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