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Journal of Virology, May 2002, p. 4350-4356, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4350-4356.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Hepatitis A Virus Suppresses Monocyte-to-Macrophage Maturation In Vitro

Sabina Wünschmann,,{dagger} Britta Becker,* and Angelika Vallbracht

Department of Virology, University of Bremen, D-28359 Bremen, Germany

Received 24 September 2001/ Accepted 28 January 2002

To analyze the pathogenetic mechanism of hematopoietic dysregulation associated with hepatitis A virus (HAV) infections, we studied the influence of HAV on monocyte (MO)-to-macrophage (MAC) maturation in vitro. Exposure of peripheral blood-derived mononuclear cells (MNC) to HAV led to diminished adherence of MO to plastic. Furthermore, HAV inhibited the ability of peripheral blood MO to differentiate toward MAC. Freshly isolated and 14-day-old MO cultures demonstrated reduced differentiation and decreased phagocytic capacity after challenge with HAV. Viral replication in MO/MAC cultures was confirmed by titration of infectious virus. We also determined the influence of HAV on the MO/MAC population in human long-term bone marrow cultures (LTBMCs). Inoculation of bone marrow MNC with HAV suppressed the establishment of an adherent stromal layer containing a reduced number of MAC. Furthermore, increased MO numbers in the nonadherent fraction of HAV-challenged LTBMCs are indicative of the disturbance of MO adherence. These findings suggest that HAV infection leads to a disorder of the mononuclear phagocytic system which may contribute to functional abnormalities of the bone marrow stroma.


* Corresponding author. Mailing address: Department of Virology, University of Bremen, Leobener Str./UFT, D-28359 Bremen, Germany. Phone: 49-421 218-7368. Fax: 49-421 218-4266. E-mail: bbecker{at}uni-bremen.de.

{dagger} Present address: Department of Internal Medicine, The University of Iowa College of Medicine, Iowa City, IA 52242.


Journal of Virology, May 2002, p. 4350-4356, Vol. 76, No. 9
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.9.4350-4356.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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