Open access

© 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license 1
http://creativecommons.org/licenses/by-nc-nd/4.0/ 2
doi:10.1016/bs.aivir.2015.03.001 3
Running title: Cyprinid herpesvirus 3 4
Title: Cyprinid herpesvirus 3, an archetype of fish alloherpesviruses 5
Authors and Affiliations 6
Maxime Boutier
1
, Maygane Ronsmans
1
, Krzysztof Rakus
1
, Joanna Jazowiecka-Rakus
1
, 7
Catherine Vancsok
1
, Léa Morvan
1
, Ma. Michelle D. Peñaranda
1
, David M. Stone
2
, Keith 8
Way
2
, Steven J. van Beurden
3
, Andrew J. Davison
4
and Alain Vanderplasschen
1
* 9
10
1
Immunology-Vaccinology (B43b), Department of Infectious and Parasitic Diseases, 11
Fundamental and Applied Research for Animals & Health (FARAH), Faculty of Veterinary 12
Medicine, University of Liège, B-4000 Liège, Belgium. 13
2
The Centre for Environment, Fisheries and Aquaculture Science, Weymouth Laboratory, 14
Barrack Road, The Nothe, Weymouth, Dorset DT4 8UB, United Kingdom. 15
3
Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16
1, 3584CL Utrecht, The Netherlands. 17
4
MRC - University of Glasgow Centre for Virus Research, 8 Church Street, Glasgow G11 18
5JR, United Kingdom. 19
20
21
*
Corresponding author. Mailing address: Immunology-Vaccinology (B43b), Department of 22
Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, 23
B-4000 Liège, Belgium. Phone: [phone] - Fax: [phone]
E-mail: [email protected] 25

Author’s contacts (see affiliations above) 26
27
Maxime Boutier: [email protected] ; [phone]
Maygane Ronsmans: [email protected] ; [phone]
Krzysztof Rakus: [email protected] ; [phone]
Joanna Jazowiecka-Rakus: [email protected] ; [phone]
Catherine Vancsok: [email protected] ; [phone]
Léa Morvan: [email protected] ; [phone]
Ma. Michelle D. Peñaranda: [email protected] ; [phone]
David M. Stone: [email protected] ; [phone]
Keith Way: [email protected] ; [phone]
Steven J. van Beurden: [email protected] ; [phone]
Andrew J. Davison: [email protected] ; [phone]
Alain Vanderplasschen (senior author): [email protected] ; [phone]
40

Cyprinid herpesvirus 3, an archetype of fish alloherpesviruses 41
1. Introduction 42
2. The order Herpesvirales 43
2.1. Phylogeny 44
2.1.1. Phylogeny of the order Herpesvirales 45
2.1.2. Phylogeny of the family Alloherpesviridae 46
2.2. Main biological properties 47
2.3. Herpesviruses infecting fish 48
3. Cyprinid herpesvirus 3 49
3.1. General description 50
3.1.1. Morphology and morphogenesis 51
3.1.2. Genome 52
3.1.3. Genotypes 53
3.1.4. Transcriptome 54
3.1.5. Structural proteome and secretome 55
3.1.6. Viral replication in cell culture 56
3.1.6.1. Cell lines permissive to CyHV-3 57
3.1.6.2. Temperature restriction 58
3.2. CyHV-3 disease 59
3.2.1. Epidemiology 60
3.2.1.1. Fish species susceptible to CyHV-3 infection 61
3.2.1.2. Geographical distribution and prevalence 62
3.2.1.3. Persistence of CyHV-3 in the natural environment 63
3.2.1.4. Use of CyHV-3 for biological control of common carp 64
3.2.2. Clinical aspects 65
3.2.2.1. Clinical signs 66
3.2.2.2. Anatomopathology 67
3.2.2.3. Histopathology 68
3.2.3. Pathogenesis 69
3.2.3.1. Productive infection 70
3.2.3.1.1. Portals of entry 71
3.2.3.1.2. Secondary sites of infection 72
3.2.3.1.3. Excretion and transmission 73
3.2.3.2. Latent infection 74
3.2.3.3. Effect of water temperature 75
3.2.4. Host-pathogen interactions 76
3.2.4.1. Susceptibility of common carp according to the developmental stage 77
3.2.4.2. Susceptibility of common carp according to host genetic background 78
3.2.4.3. Common carp innate immune response against CyHV-3 79
3.2.4.4. Common carp adaptive immune response against CyHV-3 80
3.2.4.5. CyHV-3 genes involved in immune evasion 81
3.2.5. Diagnosis 82
3.2.5.1. PCR-based methods 83
3.2.5.2. Virus isolation in cell culture 84
3.2.5.3. Immunodiagnostic methods 85
3.2.5.4. Other diagnostic assays 86
3.2.6. Vaccination 87

3.2.6.1. Natural immunization 88
3.2.6.2. Vaccine candidates 89
4. Conclusions 90
91

Abstract 92
The order Herpesvirales encompasses viruses that share structural, genetic and 93
biological properties. However, members of this order infect hosts ranging from molluscs to 94
humans. It is currently divided into three phylogenetically related families. The 95
Alloherpesviridae family contains viruses infecting fish and amphibians. There are 12 96
alloherpesviruses described to date, 10 of which infect fish. Over the last decade, Cyprinid 97
herpesvirus 3 (CyHV-3) infecting common and koi carp has emerged as the archetype of fish 98
alloherpesviruses. Since its first description in the late 1990s, this virus has induced important 99
economic losses in common and koi carp worldwide. It also has negative environmental 100
implications by affecting wild carp populations. These negative impacts and the importance of 101
the host species have stimulated studies aimed at developing diagnostic and prophylactic 102
tools. Unexpectedly, the data generated by these applied studies have stimulated interest in 103
CyHV-3 as a model for fundamental research. The present review intends to provide a 104
complete overview of the knowledge currently available on CyHV-3. 105
106
Keywords (5-10) 107
Cyprinid herpesvirus 3, CyHV-3, koi herpesvirus, KHV, common carp, fish 108
alloherpesviruses, Alloherpesviridae, Herpesvirales. 109
110
Acknowledgments 111
This work was supported by Belgian Science Policy grant R.SSTC.0454-BELVIR IAP7/45 to 112
Alain Vanderplasschen and by the Medical Research Council grant number MC_UU_12014/3 113
to Andrew Davison. 114