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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3854-3859.
Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-08-2923.


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IMMUNOBIOLOGY

Human immunodeficiency virus facilitates infection/replication of hepatitis C virus in native human macrophages

Tomasz Laskus, Marek Radkowski, Joanna Jablonska, Karen Kibler, Jeffrey Wilkinson, Debra Adair, and Jorge Rakela

From the Department of Medicine, Mayo Clinic Scottsdale, Scottsdale, AZ; and the Institute of Infectious Diseases, Medical Academy, Warsaw, Poland.

Hepatitis C virus (HCV) was found to replicate in monocytes/macrophages particularly in patients with human immunodeficiency virus type 1 (HIV-1) infection. This study was undertaken to determine whether HIV facilitates HCV infection of native human macrophages in vitro. Monocytes/macrophages were collected from healthy donors, infected with HIV M-tropic molecular clone, and then exposed to HCV-positive sera. Presence of positive and negative HCV RNA strands was determined with a novel strand-specific quantitative real-time reverse transcription–polymerase chain reaction (RT-PCR). Preceding as well as near-simultaneous infection with HIV made the macrophages more susceptible to infection with HCV; in particular, an HCV RNA–negative strand was detectable almost exclusively in the setting of concomitant HIV infection. Furthermore, HCV RNAload correlated with HIV replication level in the early stage of infection. The ratio of positive to negative strand in macrophages was lower than in control liver samples. HIV infection was also found to facilitate HCV replication in a Daudi B-cell line with engineered CD4 expression. It seems that HIV infection can facilitate replication of HCV in monocytes/macrophages either by rendering cells more susceptible to HCV infection or by increasing HCV replication. This could explain the presence of extrahepatic HCV replication in HIV-coinfected individuals.


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