Illuminating the relationship between Hepatitis C Virus and B cell disorders: Detection of viral genome in peripheral B cells using RNAscope

Authors

• KC Robichaux
• AN Henning
• V de Giorgi

Abstract

Approximately 58 million people are currently infected with Hepatitis C Virus (HCV). HCV is an enveloped, positive-strand RNA virus that primarily infects hepatocytes but has been reported to infect lymphocytes. Epidemiological studies have shown that chronic HCV infection is associated with increased risk of developing lymphoproliferative disorders, including B cell non-Hodgkin’s lymphoma. The mechanism underlying this association is unclear. It may consist of direct oncogenic effects or an indirect mechanism. Direct effects refer to potential HCV infection of B cells, while indirect mechanism includes viral interaction with cell surface receptors via chronic antigen stimulation and/or CD81 engagement. The detection of HCV replication in B cells would support the hypothesis of direct virus-mediated lymphomagenesis, where the virus could trigger oncogenic events via intracellular viral proteins. This study aims to further elucidate these mechanisms by visualizing HCV positive and negative strand RNA in B cells using RNAscope fluorescent in situ hybridization. B cells were isolated from whole blood of HCV-infected patients and healthy donors and probed for CD19 mRNA and HCV positive-strand RNA. CD19 serves as a B cell marker and HCV positive-strand RNA indicates the presence of the virus. Preliminary data show successful visualization of CD19 mRNA and HCV positive-strand RNA. Optimization of the negative-strand HCV RNA probe is ongoing. Visualization of this RNA would indicate viral proliferation within B cells. Results from this study will confirm the existence of extrahepatic reservoirs for HCV and provide more direct evidence of viral protein expression in HCV associated lymphoma.

Scientific Focus Area: Virology

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