A Role for B Cells to Transmit Hepatitis C Virus Infection.

Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination. To evaluate whether B cells play a role in HCV transmission, we assessed the ability of B cells and sera from recent (<2 years) or chronic (≥ 2 years) HCV patients to infect humanized liver chimeric mice. HCV was transmitted by B cells from chronic infected patients whereas the sera were non-infectious. In contrast, B cells from recently infected patients failed to transmit HCV to the mice, whereas all serum samples were infectious. We observed an association between circulating anti-glycoprotein E1E2 antibodies and B cell HCV transmission. Taken together, our studies provide evidence for HCV transmission by B cells, findings that have clinical implications for prophylactic and therapeutic antibody-based vaccine design.

Human hepatocytes secrete soluble CD14, a process not directly influenced by HBV and HCV infection.

BACKGROUND: Chronic hepatitis B (HBV) and hepatitis C (HCV) patients have elevated plasma levels of soluble CD14 (sCD14). We examined whether human hepatocytes produce sCD14 in vivo, and whether HBV or HCV infections influence this chimeric production. METHODS: uPA-SCID mice were transplanted with primary human hepatocytes and some animals were subsequently infected with HBV or HCV. Plasma from these mice was analyzed for the presence of human sCD14. The liver was examined via immunohistochemistry. RESULTS: A soluble form of human CD14 could be detected in the plasma from successfully transplanted mice, while it was completely absent in non-transplanted control animals. The isoform of this human sCD14 corresponded with the most abundant isoform found in human plasma. CD14 levels in circulation were not significantly different between non-infected, HBV infected and HCV infected animals. CONCLUSIONS: Our data indicate that human hepatocytes produce sCD14 in vivo, and that liver cells might be the major source of sCD14 in normal human plasma. In addition we demonstrate that HBV and HCV infections have no direct influence on the production of sCD14 by human hepatocytes in this chimeric model.

Comparison of qualitative (COBAS AMPLICOR HCV 2.0 versus VERSANT HCV RNA) and quantitative (COBAS AMPLICOR HCV monitor 2.0 versus VERSANT HCV RNA 3.0) assays for hepatitis C virus (HCV) RNA detection and quantification: impact on diagnosis and treatment of HCV infections.

Quantitative measurements of serum hepatitis C virus (HCV) RNA are becoming increasingly important in the management of HCV-infected patients. Here we compared two quantitative assays, the COBAS AMPLICOR HCV Monitor 2.0 assay (Roche Diagnostics) and the branched DNA-based VERSANT HCV RNA 3.0 assay (Bayer Diagnostics) for HCV RNA measurement in 344 samples derived from 120 patients with chronic genotype 1 HCV infection. The overall concordance between the results of the two tests was 95%, and the HCV RNA titers within the dynamic ranges of the assays correlated very well (r2=0.86). Furthermore, both tests performed equally well in determining an early viral response at week 1 or 4 during antiviral therapy. We also compared two qualitative HCV RNA detection assays: the COBAS AMPLICOR HCV 2.0 assay versus the transcription-mediated amplification (TMA)-based VERSANT HCV RNA qualitative assay. Stored samples from sustained responders to interferon-ribavirin therapy were retested by the HCV TMA assay and were found to contain no detectable HCV RNA, demonstrating complete concordance between the results of PCR and TMA. However, HCV RNA was detected by the TMA assay in end-of-treatment (ETR) samples from 33% of patients with relapses who were HCV RNA negative according to the COBAS AMPLICOR assay. This observation suggests that a TMA assay can lead to a more correct definition of the ETR response.