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Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3328-3337
Hepatitis C Virus Infection Involves CD34+
Hematopoietic Progenitor Cells in Hepatitis C Virus Chronic Carriers
Domenico Sansonno,
Claudio Lotesoriere,
Vito Cornacchiulo,
Massimo Fanelli,
Pietro Gatti,
Giuseppe Iodice,
Vito Racanelli, and
Franco Dammacco
From the Department of Biomedical Sciences and Human Oncology,
Section of Internal Medicine and Clinical Oncology, University of Bari
Medical School, Bari, Italy.
Although hepatitis C virus (HCV) mainly affects hepatocytes,
infection is widespread and involves immunologically privileged sites.
Whether lymphoid cells represent further targets of early HCV
infection, or whether other cells in the hematopoietic microenvironment may serve as a potential virus reservoir, is still unclear. We studied
whether pluripotent hematopoietic CD34+ cells support
productive HCV infection and can be used to establish an in vitro
infection system for HCV. Six patients were selected as part of a
cohort of HCV chronic carriers who developed a neoplastic disease.
Reverse transcriptase-polymerase chain reaction (RT-PCR) and branched
DNA signal amplification assays were used to detect and quantitate HCV
RNA in extracted nucleic acids from purified bone marrow and peripheral
blood CD34+ cells. Direct in situ RT-PCR, flow cytometry
analysis, and immunocytochemistry were applied to demonstrate specific
viral genomic sequences and structural and nonstructural virus-related
proteins in intact cells. Results indicated that both positive and
negative HCV RNA strands and viral proteins were present in
CD34+ cells from all HCV-positive patients and in none of
the controls. Additional experiments showed that a complete viral cycle
took place in CD34+ cells in vitro. Spontaneous increases
in viral titers indicated that virions were produced by infected
hematopoietic progenitor cells. To further define the cellular tropism,
we attempted to infect CD34+ cells in vitro. We were
unable to demonstrate viral uptake by cells. These findings suggest
that HCV replication can occur in the early differentiation stages of
hematopoietic progenitor cells, and that they may be an important
source of virus production.
© 1998 by The American Society of Hematology.
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