Polyomaviridae!
Date: 2 سال قبل
author: AmirAbad
Polyomaviridae
Polyomaviruses are composed
of nonenveloped capsids with a circular double-stranded DNA (dsDNA) genome of
approximately 5,000 base pairs containing a single origin of replication and a
bidirectional promoter that drives expression of messenger RNA (mRNA)
transcripts encoding five to nine proteins.
CLASSIFICATION
The human Alpha
polyomaviruses comprise MCPyV, as well as TSPyV, HPyV9, and New Jersey (NJPyV).
The Beta polyomaviruses include SV40 and the human JCPyV, BKPyV, KIPyV, and
WUPyV polyomaviruses. The Gamma polyomaviruses contain species isolated from
birds.
VIRION STRUCTURE
Polyomavirus virions are
nonenveloped, 45- to 50-nm particles consisting of two or three virally encoded
capsid proteins. All viruses have the major capsid protein Vp1 and the minor
protein Vp2, and some also have Vp3 derived from an internal start site within
the VP2 gene.The virions encapsidate a circular dsDNA genome wrapped with
cellular histones H2A, H2B, H3, and H4.
The polyomavirus capsid
contains 360 molecules of Vp1 arranged as 72 pentamers, each containing five
molecules of Vp1 and one molecule of Vp2 or Vp3. Only the Vp1 molecule is
exposed on the surface of the capsid.
GENOME STRUCTURE AND
ORGANIZATION
The polyomavirus dsDNA
circular genome contains approximately 5,000 base pairs and can be divided into
three parts: the early viral gene region (EVGR) encoding genes that are
expressed prior to the onset of DNA replication; the late viral gene region
(LVGR) encoding genes expressed after viral DNA replication begins; and the
regulatory region, also called noncoding control region (NCCR), containing the
origin of viral DNA replication and the promoters and enhancers for early and
late viral genes
PATHOGENESIS AND PATHOLOGY
JCPyV is able to
productively infect tonsillar stromal cells in culture with efficiency nearly
comparable to human glial cells. JCPyV DNA has also been found in lymphoid
tissues including bone marrow and spleen. JCPyV DNA has been identified in
tonsil stromal cells and in B cells isolated from tonsils. The ability of JCPyV
to infect tonsillar stromal cells in culture and the presence of JCPyV DNA in
tonsil tissue suggest the possibility that the initial infection could occur in
these tissues as well. BKPyV has been detected in lung tissue from one case of
interstitial pneumonia in a hematopoietic stem cell transplant (HSCT) patient
and in the respiratory tract and tonsil tissue in another, as well as in
salivary glands, and can replicate in salivary cells in culture. This, together
with the observation that the majority of the population in both developed and
developing regions of the world seroconverts in early to mid-childhood, would
support a respiratory or oropharyngeal–gastrointestinal route of transmission.
127 By the same token, it is surprising that other viruses were not reported,
some of which had been proposed to be associated with respiratory symptoms or
febrile tonsillitis such as BK virus and other polyomaviruses.
BKPyV-Associated Diseases
BKPyV is recognized as the main etiological
agent of polyomavirus-associated nephropathy (PyVAN), polyomavirus-associated
hemorrhagic cystitis (PyVHC), and the increasingly recognized
polyomavirus-associated urothelial cancer (PyVUC). BKPyV has also been
implicated in rare cases of ureteric stenosis, pneumonitis, encephalitis,
retinitis, vasculitis, and multiorgan involvement, 130 but little is known
about their prevalence, risk factors, and pathogenesis.
JCPyV is the main
etiological agent of PML. Other neurological manifestations are granule cell
neuronopathy in the cerebellum, encephalopathy targeting cortical pyramidal
neurons, as well as meningitis and encephalitis. Despite its major tropism for
the renourinary tract and persistent shedding in immunocompetent persons, JCPyV
is a rare cause of PyVAN in kidney transplant patients. In addition, an
association of JCPyV infection with malignancies in the brain, in lymph nodes,
and in gastrointestinal tract has been reported.
Diagnosis
The detection of BK &
JC DNA by quantitative PCR is the most frequently employed approach for the
diagnosis of PyVAN AND JCPyV infection, and serial measurements of viral DNA
has largely replaced other assays for virologicalmonitoring patients at risk
for invasive PyVAN and JCPyV infection.
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