Barriers to infection of human cells by feline leukemia virus: insights into resistance to zoonosis

Terry, A., Kilbey, A., Naseer, A., Levy, L. S., Ahmad, S., Watts, C., Mackay, N., Cameron, E. , Wilson, S. and Neil, J. C. (2017) Barriers to infection of human cells by feline leukemia virus: insights into resistance to zoonosis. Journal of Virology, 91(5), e02119-16. (doi: 10.1128/JVI.02119-16) (PMID:28031367) (PMCID:PMC5309941)

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Abstract

The human genome displays a rich fossil record of past gamma-retrovirus infections, yet no current epidemic is evident, despite environmental exposure to viruses that infect human cells in vitro. Feline leukemia viruses (FeLVs) rank high on this list, but domestic or workplace exposure has not been associated with detectable serological responses. Non-specific inactivation of gamma-retroviruses by serum factors appears insufficient to explain these observations. To investigate further we explored the susceptibility of primary and established human cell lines to FeLV-B, the most likely zoonotic variant. Fully permissive infection was common in cancer-derived cell lines, but was also a feature of non-transformed keratinocytes and lung fibroblasts. Cells of haematopoietic origin were less generally permissive and formed discrete groups on the basis of high or low intracellular protein expression and virion release. Potent repression was observed in primary human blood mononuclear cells and a subset of leukemia cell lines. However, the early steps of reverse transcription and integration appear to be unimpaired in non-permissive cells. FeLV-B was subject to G->A hypermutation with a predominant APOBEC3G signature in partially permissive cells but was not mutated in permissive cells or in non-permissive cells that block secondary viral spread. Distinct cellular barriers that protect primary human blood cells are likely to be important in protection against zoonotic infection with FeLV.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cameron, Professor Ewan and Neil, Professor James and Wilson, Professor Sam and Naseer, Dr Asif and Kilbey, Dr Anna and Watts, Dr Ciorsdaidh and Terry, Mrs Anne
Authors: Terry, A., Kilbey, A., Naseer, A., Levy, L. S., Ahmad, S., Watts, C., Mackay, N., Cameron, E., Wilson, S., and Neil, J. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
College of Science and Engineering > School of Chemistry
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:28 December 2016
Copyright Holders:Copyright © 2016 Terry et al.
First Published:First published in Journal of General Virology 91(5): e02119-16
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
539394New Approaches to Modelling Human LeukaemiaEwan CameronBloodwise (LLR)13046VET - PATHOLOGY, PUBLIC H & DISEASE INV
539151New Approaches to Modelling Human LeukaemiaJames NeilCancer Research UK (CAN-RES-UK)11951MVLS III - CENTRE FOR VIRUS RESEARCH