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.
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.
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Chen S
CS
Tan
Bruce J
BJ
Dezube
Parul
P
Bhargava
Patrick
P
Autissier
Christian
C
Wüthrich
Janice
J
Miller
Igor J
IJ
Koralnik
D015703:Antigens, CD / Q000032:analysis; D001769:Blood / Q000821:virology; D001853:Bone Marrow / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis*; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000097:blood / Q000652:urine / Q000821:virology*; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D014556:Urine / Q000821:virology; D014764:Viral Proteins / Q000032:analysis*; D017735:Virus Latency
D015703:Antigens, CD; D004279:DNA, Viral; D014764:Viral Proteins