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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Virol
2015 ; 89
(2
): 1340-7
Nephropedia Template TP
gab.com Text
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JC virus quasispecies analysis reveals a complex viral population underlying
progressive multifocal leukoencephalopathy and supports viral dissemination via
the hematogenous route
#MMPMID25392214
Van Loy T
; Thys K
; Ryschkewitsch C
; Lagatie O
; Monaco MC
; Major EO
; Tritsmans L
; Stuyver LJ
J Virol
2015[Jan]; 89
(2
): 1340-7
PMID25392214
show ga
Opportunistic infection of oligodendrocytes by human JC polyomavirus may result
in the development of progressive multifocal encephalopathy in immunocompromised
individuals. Neurotropic JC virus generally harbors reorganized noncoding control
region (NCCR) DNA interspersed on the viral genome between early and late coding
genes. By applying 454 sequencing on NCCR DNA amplified from body fluid samples
(urine, plasma, and cerebrospinal fluid [CSF]) from 19 progressive multifocal
leukoencephalopathy (PML) patients, we attempted to reveal the composition of the
JC polyomavirus population (the quasispecies, i.e., the whole of the consensus
population and minor viral variants) contained in different body compartments and
to better understand intrapatient viral dissemination. Our data demonstrate that
in the CSF of PML patients, the JC viral population is often a complex mixture
composed of multiple viral variants that contribute to the quasispecies. In
contrast, urinary JC virus highly resembled the archetype virus, and urine most
often did not contain minor viral variants. It also appeared that archetype JC
virus could sporadically be identified in PML patient brain, although selection
of rearranged JC virus DNA was favored. Comparison of the quasispecies from
different body compartments within a given patient suggested a strong correlation
between the viral population in plasma and CSF, whereas the viral population shed
in urine appeared to be unrelated. In conclusion, it is shown that the
representation of viral DNA in the CSF following the high-level DNA replication
in the brain underlying PML has hitherto been much underestimated. Our data also
underscore that the hematogenous route might play a pivotal role in viral
dissemination from or toward the brain. IMPORTANCE: For the first time, the JC
polyomavirus population contained in different body compartments of patients
diagnosed with progressive multifocal encephalopathy has been studied by deep
sequencing. Two main findings came out of this work. First, it became apparent
that the complexity of the viral population associated with PML has been highly
underestimated so far, suggestive of a highly dynamic process of reorganization
of the noncoding control region of JC polyomavirus in vivo, mainly in CSF and
blood. Second, evidence showing viral dissemination from and/or toward the brain
via the hematogenous route was provided, confirming a hypothesis that was
recently put forward in the field.