Abstract
GB virus B (GBV-B) is a new world monkey-associated flavivirus used to model acute hepatitis C virus (HCV) infection. Critical for evaluation of antiviral or vaccine approaches is an understanding of the effect of HCV on the liver at different stages of infection. In the absence of longitudinal human tissue samples at defined time points, we have characterized changes in tamarins. As early as 2 weeks post-infection histological changes were noticeable, and these were established in all animals by 6 weeks. Despite high levels of liver-associated viral RNA, there was reversal of hepatic damage on clearance of peripheral virus though fibrosis was demonstrated in four tamarins. Notably, viral RNA burden in the liver dropped to near undetectable or background levels in all animals which underwent a second viral challenge, highlighting the efficacy of the immune response in removing foci of replication in the liver. These data add to the knowledge of GBV-B infection in New World primates which can offer attractive systems for the testing of prophylactic and therapeutic treatments and the evaluation of their utility in preventing or reversing liver pathology.
Highlights
Infection with hepatitis C virus (HCV) remains a worldwide public health issue
Purpose‐bred, weaned, red‐bellied tamarins (Saguinus labiatus) were housed, and all animal procedures were performed in strict accordance with UK Home Office guidelines, under a licence granted to the host establishment by the Secretary of State for the Home Office which approved the work described
Of the four tamarins in Group D only a male, T21, demonstrated liver damage, with portal tract expansion and extramedullary erythropoiesis (EME) infiltration expanding into the parenchyma
Summary
Infection with hepatitis C virus (HCV) remains a worldwide public health issue. While there have been recent advances in novel direct‐ acting antivirals (DAA), the availability and accessibility of these globally is not certain. If the mode of control in acute infection was fully understood, it would provide a guide for the rational design of effective vaccine and treatment strategies Such a description would need to include liver pathology as well as events detectable in the peripheral blood. Experimental infection with GBV‐B results in high viremia, typically followed by a viral clearance from the periphery within 18 weeks of infection (reviewed in Reference 2); rechallenge following clearance is typically readily controlled.[3] The potential utility of a New World primate Hepacivirus model in the investigation of liver‐associated pathology concomitant with peripheral viremia is highly important. We have demonstrated that it could be utilized to evaluate the ability of novel prophylactic and therapeutic treatments to prevent or reverse viremia and liver damage Such information could inform the clinical application of these treatments in humans with HCV infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
