GB Virus B and Hepatitis C Virus, distantly related Hepaciviruses, share an entry factor, Claudin-1.

Toon, K. , Kalemera, M. D., Palor, M., Rose, N. J., Takeuchi, Y., Grove, J. and Mattiuzzo, G. (2023) GB Virus B and Hepatitis C Virus, distantly related Hepaciviruses, share an entry factor, Claudin-1. Journal of Virology, 97(7), e00469-23. (doi: 10.1128/jvi.00469-23) (PMID:37310242) (PMCID:PMC10373534)

Abstract

Due to increased and broadened screening efforts, the last decade has seen a rapid expansion in the number of viral species classified into the Hepacivirus genus. Conserved genetic features of hepaciviruses suggest that they have undergone specific adaptation and have evolved to hijack similar host proteins for efficient propagation in the liver. Here, we developed pseudotyped viruses to elucidate the entry factors of GB virus B (GBV-B), the first hepacivirus described in an animal after hepatitis C virus (HCV). GBV-B-pseudotyped viral particles (GBVBpp) were shown to be uniquely sensitive to the sera of tamarins infected with GBV-B, validating their usefulness as a surrogate for GBV-B entry studies. We screened GBVBpp infection of human hepatoma cell lines that were CRISPR/Cas9 engineered to ablate the expression of individual HCV receptors/entry factors and found that claudin-1 is essential for GBV-B infection, indicating the GBV-B and HCV share an entry factor. Our data suggest that claudin-1 facilitates HCV and GBV-B entry through distinct mechanisms since the former requires the first extracellular loop and the latter is reliant on a C-terminal region containing the second extracellular loop. The observation that claudin-1 is an entry factor shared between these two hepaciviruses suggests that the tight junction protein is of fundamental mechanistic importance during cell entry.

• Item Type: Articles
• Additional Information: K.T. was supported by a Ph.D. studentship through the National Institute for Biological Standards and Control, the Medicines and Healthcare Products Regulatory Agency. J.G. is supported by a Sir Henry Dale fellowship from the Wellcome Trust and Royal Society(107653/Z/15/A) and by the Medical Research Council (MC_UU_12014).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Grove, Dr Joe and Toon, Dr Kamilla
• Authors: Toon, K., Kalemera, M. D., Palor, M., Rose, N. J., Takeuchi, Y., Grove, J., and Mattiuzzo, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of Virology
• Publisher: American Society for Microbiology
• ISSN: 0022-538X
• ISSN (Online): 1098-5514
• Published Online: 13 June 2023
• Copyright Holders: Copyright © 2023 Crown
• First Published: First published in Journal of Virology 97(7):e0046923
• Publisher Policy: Reproduced under a Creative Commons licence