Changes in immune cell populations in the periphery and liver of GBV-B-infected and convalescent tamarins (Saguinus labiatus)

Abstract

Flaviviruses related to hepatitis C virus (HCV) in suitable animal models may provide further insight into the role that cellular immunity contributes to spontaneous clearance of HCV. We characterised changes in lymphocyte populations in tamarins with an acute GBV-B infection, a hepatitis virus of the flaviviridae. Major immune cell populations were monitored in peripheral and intra-hepatic lymphocytes at high viraemia or following a period when peripheral virus was no longer detected. Limited changes in major lymphocyte populations were apparent during high viraemia; however, the proportions of CD3(+) lymphocytes decreased and CD20(+) lymphocytes increased once peripheral viraemia became undetectable. Intrahepatic lymphocyte populations increased at both time points post-infection. Distinct expression patterns of PD-1, a marker of T-cell activation, were observed on peripheral and hepatic lymphocytes; notably there was elevated PD-1 expression on hepatic CD4(+) T-cells during high viraemia, suggesting an activated phenotype, which decreased following clearance of peripheral viraemia. At times when peripheral vRNA was not detected, suggesting viral clearance, we were able to readily detect GBV-B RNA in the liver, indicative of long-term virus replication. This study is the first description of changes in lymphocyte populations during GBV-B infection of tamarins and provides a foundation for more detailed investigations of the responses that contribute to the control of GBV-B infection.

Keywords: 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; APC; Acute viral hepatitis; CTLA4; DMSO; EGTA; FITC; Fluorescein isothiocyanate; GB virus B; GBV-B; HBSS; HCV; HEPES; Hank's balanced salt solution; IFN; IHL; IVT; Immune cell; MFI; MHC; NK; NS; PD-1; PD1-L1; PE; RPMI; Roswell Park Memorial Institute medium; allophycocyanin; cytotoxic T lymphocyte antigen-4; dimethyl sulphoxide; ethylene glycol tetraacetic acid; ge; genome equivalents; hepatitis C virus; in vitro transcription; interferon; intrahepatic lymphocytes; major histocompatibility complex; median fluorescence intensity; natural killer; non-structural; phycoerythrin; programmed death receptor-1; programmed death receptor-1 ligand; qRT-PCR; quantitative reverse transcriptase polymerase chain reaction; vRNA; viral ribonucleic acid.