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. 2009 Mar 15;199(6):881-8.
doi: 10.1086/597117.

Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation

Chen S Tan  1 , Bruce J Dezube, Parul Bhargava, Patrick Autissier, Christian Wüthrich, Janice Miller, Igor J Koralnik
Affiliations

Detection of JC virus DNA and proteins in the bone marrow of HIV-positive and HIV-negative patients: implications for viral latency and neurotropic transformation

Chen S Tan et al. J Infect Dis. .

Abstract

Background: We sought to determine the prevalence of JC virus (JCV) in bone marrow samples from human immunodeficiency virus (HIV)-positive and HIV-negative patients and to determine whether bone marrow is a site of latency and neurotropic transformation of JCV, the agent of progressive multifocal leukoencephalopathy (PML).

Methods: We collected bone marrow aspirates, archival bone marrow samples, and blood and urine samples from 75 HIV-negative and 47 HIV-positive patients without PML as well as bone marrow and urine or kidney samples from 8 HIV-negative and 15 HIV-positive patients with PML. Samples were tested for JCV DNA by quantitative polymerase chain reaction and for JCV protein expression by immunohistochemical analysis. JCV regulatory regions (RRs) were characterized by sequencing.

Results: JCV DNA was detected in bone marrow samples from 10 (13%) of 75 and 22 (47%) of 47 of the HIV-negative and HIV-positive patients without PML, respectively, compared with 3 (38%) of 8 and 4 (27%) of 15 of the HIV-negative and HIV-positive patients with PML. JCV DNA (range, 2-1081 copies/microg of cellular DNA) was detected in multiple leukocyte subpopulations of blood and bone marrow samples. JCV large T antigen, but not VP1 capsid protein, was expressed in bone marrow plasma cells. Bone marrow JCV RR sequences were similar to those usually found in the brains of patients with PML.

Conclusions: Bone marrow is an important reservoir and a possible site of neurotropic transformation for JCV.

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Figures

Figure 1
Figure 1
Double immunostaining for JCV T Ag and CD138+ plasma cells in archival bone marrow sample from an HIV-POSITIVE patient without PML. Three CD138+ plasma cells (red) express JCV T Ag (brown, arrows) next to one uninfected plasma cell (red only, asterisk), and one T Ag+ CD138-negative cell (brown only, arrowhead). Bar=50μm
See this image and copyright information in PMC

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