Development of reverse genetics systems and investigation of host response antagonism and reassortment potential for Cache Valley and Kairi viruses, two emerging orthobunyaviruses of the Americas

Dunlop, J. I. et al. (2018) Development of reverse genetics systems and investigation of host response antagonism and reassortment potential for Cache Valley and Kairi viruses, two emerging orthobunyaviruses of the Americas. PLoS Neglected Tropical Diseases, 12(10), e0006884. (doi:10.1371/journal.pntd.0006884) (PMID:30372452) (PMCID:PMC6245839)

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Abstract

Orthobunyaviruses such as Cache Valley virus (CVV) and Kairi virus (KRIV) are important animal pathogens. Periodic outbreaks of CVV have resulted in the significant loss of lambs on North American farms, whilst KRIV has mainly been detected in South and Central America with little overlap in geographical range. Vaccines or treatments for these viruses are unavailable. One approach to develop novel vaccine candidates is based on the use of reverse genetics to produce attenuated viruses that elicit immune responses but cannot revert to full virulence. The full genomes of both viruses were sequenced to obtain up to date genome sequence information. Following sequencing, minigenome systems and reverse genetics systems for both CVV and KRIV were developed. Both CVV and KRIV showed a wide in vitro cell host range, with BHK-21 cells a suitable host cell line for virus propagation and titration. To develop attenuated viruses, the open reading frames of the NSs proteins were disrupted. The recombinant viruses with no NSs protein expression induced the production of type I interferon (IFN), indicating that for both viruses NSs functions as an IFN antagonist and that such attenuated viruses could form the basis for attenuated viral vaccines. To assess the potential for reassortment between CVV and KRIV, which could be relevant during vaccination campaigns in areas of overlap, we attempted to produce M segment reassortants by reverse genetics. We were unable to obtain such viruses, suggesting that it is an unlikely event.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilkie, Dr Gavin and Modha, Ms Sejal and Dunlop, Dr James and Da Silva Filipe, Dr Ana and Vattipally, Dr Sreenu and Navarro, Dr Aitor and Li, Dr Ping and Brennan, Dr Benjamin and Hughes, Dr Joseph and Mair, Mr Daniel and Tong, Dr Lily and Elliott, Professor Richard and Kohl, Professor Alain and Szemiel, Dr Agnieszka
Authors: Dunlop, J. I., Szemiel, A. M., Navarro, A., Wilkie, G. S., Tong, L., Modha, S., Mair, D., Sreenu, V. B., Da Silva Filipe, A., Li, P., Huang, Y.-J. S., Brennan, B., Hughes, J., Vanlandingham, D. L., Higgs, S., Elliott, R. M., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2018 Dunlop et al.
First Published:First published in PLoS Neglected Tropical Diseases 12(10): e0006884
Publisher Policy:Reproduced under a Creative Commons License
Data DOI:10.5525/gla.researchdata.599

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656551Arbovirus interactions with arthropod hostsAlain KohlMedical Research Council (MRC)MC_UU_12014/8MVLS III - CENTRE FOR VIRUS RESEARCH
UNSPECIFIEDUNSPECIFIEDUNSPECIFIEDUNSPECIFIEDUNSPECIFIEDSPHSU8UNSPECIFIED