Equine herpesviruses (EHV): from EHV-1 to EHV-5 … herpesvirus 4 Equine rhinopneumonitis (Equine...

Equine herpesviruses (EHV): Equine herpesviruses (EHV): from EHVfrom EHV--1 to EHV1 to EHV--5 and more.5 and more.

What does tell us the numberWhat does tell us the numberwith regards to clinical signs and with regards to clinical signs and

epidemiology?epidemiology?Etienne THIRYEtienne THIRY

Virology and viral diseasesVirology and viral diseasesDepartment of infectious and parasitic diseasesDepartment of infectious and parasitic diseases

Faculty of veterinary medicineFaculty of veterinary medicineUniversity of LiègeUniversity of Liège

The faculty of veterinary medicineUniversity of Liège (Belgium)

�� IntroductionIntroduction–– Herpesviruses: structure and classificationHerpesviruses: structure and classification–– Equine alphaEquine alpha-- and gammaherpesvirusesand gammaherpesviruses

�� Respiratory infection with EHVRespiratory infection with EHV--1 and EHV1 and EHV--44�� Abortion caused by EHVAbortion caused by EHV--11�� Myeloencephalopathy mediated by EHVMyeloencephalopathy mediated by EHV--11�� Genital and respiratory infection with EHVGenital and respiratory infection with EHV--33�� Equine gammaherpesviruses: EHVEquine gammaherpesviruses: EHV--2 and EHV2 and EHV--55�� Other herpesviruses in donkey and other equidsOther herpesviruses in donkey and other equids�� ConclusionsConclusions

�Viral enzymes involved in nucleic acid metabolism and protein maturation�Viral DNA synthesis and capsid formation in the nucleus �Productive infection leading almost always to the cell death�Establishment of latent infections

Glycoprotein

Tegument

Nucleocapsid

Envelope

Herpesviridae: general properties

DNA

The family Herpesviridae

�� AlphaherpesvirinaeAlphaherpesvirinae–– Epithelial and neuronal tropismEpithelial and neuronal tropism–– Latency in neurons (but also in lymphocytes)Latency in neurons (but also in lymphocytes)

�� BetaherpesvirinaeBetaherpesvirinae–– CytomegalovirusCytomegalovirus

�� GammaherpesvirinaeGammaherpesvirinae–– Lymphocytic tropismLymphocytic tropism–– Latency in mononuclear cellsLatency in mononuclear cells

HHV-1HHV-2HHV-3

BoHV-1

EHV-1

EHV-4Su

HV-1M

DVIL

TVHHV-5M

CMV

HHV-6HHV-7ElH

V-1HHV-4M

uHV-4

BoHV-4

CeHV-17

HHV-8

SaHV-2

OsHV-1

IcHV-1

SalH

V-1Sa

lHV-2

RaHV-1

RaHV-2

80-120 million years

180-210 million years

400 million years

(Davison, 2002)

� �

γγγγ

Horse and related species

donkey

zebra

African wild ass

Alphaherpesviruses

Asinine herpesvirus 3Asinine herpesvirus 3, , homologous to EHVhomologous to EHV--11Equid herpesvirus 8Equid herpesvirus 8

Thomson gazella (encephalitis)Thomson gazella (encephalitis)Zebra (subclinical infection)Zebra (subclinical infection)

Equid herpesvirus 9Equid herpesvirus 9

Asinine herpesvirus 1Asinine herpesvirus 1, , homologous to EHVhomologous to EHV--33Equid herpesvirus 6Equid herpesvirus 6

Coital exanthemaCoital exanthemaEquid herpesvirus 3Equid herpesvirus 3

Equine rhinopneumonitisEquine rhinopneumonitisEquid herpesvirus 4Equid herpesvirus 4

(Equine rhinopneumonitis), (Equine rhinopneumonitis), Abortion, MyeloencephalopathyAbortion, MyeloencephalopathyEquid herpesvirus 1Equid herpesvirus 1

Gammaherpesviruses

DNA in blood cells; related to EHVDNA in blood cells; related to EHV--2 and EHV2 and EHV--55Zebra herpesvirusZebra herpesvirus

Subclinical infectionSubclinical infectionEquid herpesvirus 5Equid herpesvirus 5

Associated with letal pneumonitis; Associated with letal pneumonitis; related to EHVrelated to EHV--22Asinine herpesvirus 5Asinine herpesvirus 5

DNA in blood cells; related to EHVDNA in blood cells; related to EHV--2 and EHV2 and EHV--55Wild ass herpesvirusWild ass herpesvirus

Asinine herpesvirus 2Asinine herpesvirus 2Equid herpesvirus 7Equid herpesvirus 7

Related to EHVRelated to EHV--2 and EHV2 and EHV--55Asinine herpesvirus 6Asinine herpesvirus 6

Associated with letal pneumonitis; Associated with letal pneumonitis; related to EHVrelated to EHV--22Asinine herpesvirus 4Asinine herpesvirus 4

Subclinical infection; respiratory disease (?)Subclinical infection; respiratory disease (?)Equid herpesvirus 2Equid herpesvirus 2

Respiratory infection with EHV-4 or EHV-1: equine rhinopneumonitis

�� EHVEHV--1 and EHV1 and EHV--4: closely related4: closely related�� Acute upper respiratory disease Acute upper respiratory disease

(rhinitis)(rhinitis)�� High prevalenceHigh prevalence

–– Infection during the first year of lifeInfection during the first year of life–– Numerous subclinical infectionsNumerous subclinical infections–– Respiratory outbreaks in twoRespiratory outbreaks in two--years years

old horsesold horses»» In training centresIn training centres

�� General signs: fever and General signs: fever and anorexiaanorexia

�� Respiratory signs: serous to Respiratory signs: serous to mucupurulent nasal dischargemucupurulent nasal discharge

�� BronchoBroncho--pneumonia:pneumonia:complicationcomplication ofof rhinitisrhinitis

Abortion caused by EHV-1

�� EHVEHV--1 1 –– First 2/3 of pregnancy: risk of myeloencephalopathyFirst 2/3 of pregnancy: risk of myeloencephalopathy–– Last 1/3 of pregnancy (6Last 1/3 of pregnancy (6--11 months): risk of abortion11 months): risk of abortion

�� Winter timeWinter time�� First abortion contaminates the other maresFirst abortion contaminates the other mares

–– Abortion storm: very rareAbortion storm: very rare–– Sporadic occurrenceSporadic occurrence

�� No clinical sign in the mareNo clinical sign in the mare

Abortion caused by EHV-1

�� Aborted foetuses before 6 monthsAborted foetuses before 6 months–– Diffuse cellular necrosis, without Diffuse cellular necrosis, without

inflammationinflammation

�� Aborted foetuses after 6 monthsAborted foetuses after 6 months–– Macroscopic inflammatoryMacroscopic inflammatory lesionslesions

EHV-1 : neonatal disease

�� Infection in late gestationInfection in late gestation�� Perinatal systemic diseasePerinatal systemic disease�� Fever, depressionFever, depression�� LymphopeniaLymphopenia�� Respiratory distressRespiratory distress�� DeathDeath

Myeloencephalopathy mediated by EHV-1�� After reinfection: After reinfection:

–– In the presence of antibodiesIn the presence of antibodies–– Immunopathology (?)Immunopathology (?)

�� After infection or reAfter infection or re--infectioninfection–– Vasculitis, thrombosis and anoxiaVasculitis, thrombosis and anoxia–– In spinal chordIn spinal chord

�� LatencyLatency�� Low incidenceLow incidence�� Sporadic or Sporadic or epidemicepidemic formform�� Association with abortion or Association with abortion or

respiratory formrespiratory form�� No general signNo general sign�� Ataxia, posterior paresis, paralysisAtaxia, posterior paresis, paralysis�� Full or partial recovery, or death Full or partial recovery, or death

or euthanasiaor euthanasia

Equine coital exanthema (EHV-3)

�� EHVEHV--3: no antigenic relationship3: no antigenic relationshipwith any other equid herpesviruswith any other equid herpesvirus

�� Thermosensitive virusThermosensitive virus�� Venereal infectionVenereal infection

–– Infections of stallions and maresInfections of stallions and mares�� Isolated from nasal swabsIsolated from nasal swabs�� Local dissemination of the virusLocal dissemination of the virus�� Latent virus (undetermined site of latency)Latent virus (undetermined site of latency)�� Papular then vesicular lesions on the mucosaPapular then vesicular lesions on the mucosa�� No general clinical signNo general clinical sign

Equine gammaherpesviruses: EHV-2 and EHV-5

��Equid herpesvirus 2 Equid herpesvirus 2 (EHV(EHV--2)2)

–– Respiratory infectionRespiratory infection–– LymphotropismLymphotropism–– Latency in B lymphocytes,Latency in B lymphocytes,

lymph nodes, CNSlymph nodes, CNS–– WidespreadWidespread–– Numerous subclinical Numerous subclinical

infectionsinfections–– Associated with acuteAssociated with acute

upper respiratory signsupper respiratory signs

��Equid herpesvirus 5 Equid herpesvirus 5 (EHV(EHV--5)5)

–– Respiratory infectionRespiratory infection–– LymphotropismLymphotropism–– Latency in mononuclearLatency in mononuclear

cellscells–– Widespread Widespread –– Subclinical infectionsSubclinical infections

–– No association with any No association with any diseasedisease

–– Closely related to EHVClosely related to EHV--22

Alphaherpesviruses

Thomson gazella Thomson gazella (encephalitis)(encephalitis)Zebra (subclinical Zebra (subclinical infection)infection)

Equid Equid herpesvirus 9herpesvirus 9

Asinine herpesvirus 3Asinine herpesvirus 3, , homologous to EHVhomologous to EHV--11


Asinine herpesvirus 1Asinine herpesvirus 1, , homologous to EHVhomologous to EHV--33


Gammaherpesviruses

Associated with letal Associated with letal pneumonitis; related to EHVpneumonitis; related to EHV--22

Asinine Asinine herpesvirus 5herpesvirus 5

Asinine herpesvirus 2Asinine herpesvirus 2Equid Equid herpesvirus 7herpesvirus 7

Related to EHVRelated to EHV--2 and EHV2 and EHV--55Asinine Asinine herpesvirus 6herpesvirus 6

Associated with letal Associated with letal pneumonitis; related to EHVpneumonitis; related to EHV--22

Asinine Asinine herpesvirus 4herpesvirus 4

DNA in blood cells; related DNA in blood cells; related to EHVto EHV--2 and EHV2 and EHV--55

Wild ass Wild ass herpesvirusherpesvirus

DNA in blood cells; related to DNA in blood cells; related to EHVEHV--2 and EHV2 and EHV--55

Zebra Zebra herpesvirusherpesvirus

Conclusions�� The number of equine herpesviruses is increasingThe number of equine herpesviruses is increasing�� Besides the «Besides the « wellwell--knownknown » equine herpesviruses:» equine herpesviruses:

–– Newly recognized viruses in other equidsNewly recognized viruses in other equids–– Cross relationships between several herpesviruses Cross relationships between several herpesviruses

(asinine & equine)(asinine & equine)�� Crossing of the species barrierCrossing of the species barrier

–– Thomson gazella: encephalitis by EHVThomson gazella: encephalitis by EHV--99–– New world camelids: encephalitis (blindness) by EHVNew world camelids: encephalitis (blindness) by EHV--11

�� Complex pathogenesisComplex pathogenesis–– EHVEHV--1: epithelial cells, lymphocytes, endothelial cells1: epithelial cells, lymphocytes, endothelial cells–– EHVEHV--3: genital versus respiratory infection3: genital versus respiratory infection

�� Further work of the pathogenesisFurther work of the pathogenesis

�� Benoît Benoît Muylkens:Muylkens: herpesvirus recombination, miRNA in herpesvirusesherpesvirus recombination, miRNA in herpesviruses

�� JulienJulien Thiry:Thiry: ruminant alphaherpesviruses, new adjuvantsruminant alphaherpesviruses, new adjuvants

�� Angélique Zicola: Angélique Zicola: feline calicivirus, dog and cat enteric virusesfeline calicivirus, dog and cat enteric viruses

�� The «The « norovirusnorovirus » team: Alexandra Scipioni (» team: Alexandra Scipioni (bovine noroviruses), bovine noroviruses), Axel Mauroy (Axel Mauroy (virusvirus--like particles, noroviruslike particles, norovirus--cell interaction), cell interaction), Elisabeth Mathijs (Elisabeth Mathijs (molecular epidemiology of noroviruses)molecular epidemiology of noroviruses)

�� The «The « bluetonguebluetongue » team at the faculty: Claude Saegerman» team at the faculty: Claude Saegerman(epidemiology)(epidemiology), Bertrand Losson , Bertrand Losson (entomology)(entomology), Hugues Guyot, Hugues Guyot(clinic)(clinic), Axel Mauroy , Axel Mauroy (pathogenesis)(pathogenesis)

�� The technical team: Lorène Dams, Dominique Ziant, The technical team: Lorène Dams, Dominique Ziant, Christine Thys and the studentsChristine Thys and the students

ACKNOWLEDGEMENTS

�� Herpesvirus network:Herpesvirus network:–– Vincenzo Cuteri (Camerino)Vincenzo Cuteri (Camerino)–– Team of Bari: Canio Buonavoglia, Maria TempestaTeam of Bari: Canio Buonavoglia, Maria Tempesta

and their collaboratorsand their collaborators–– INTA (Argentinan) team: Alejandra RomeraINTA (Argentinan) team: Alejandra Romera

and her collaborators, Maria Barrandeguyand her collaborators, Maria Barrandeguy�� Norovirus network: Jan Vinje (Norovirus network: Jan Vinje (CDC AtlantaCDC Atlanta), Lieve Herman (), Lieve Herman (MelleMelle),),

Katelijne Dierick (Katelijne Dierick (BrusselsBrussels), Mieke Uyttendaele (), Mieke Uyttendaele (GhentGhent), ), Georges Daube (Georges Daube (LiègeLiège))

�� Bluetongue network: Kris De Clercq Bluetongue network: Kris De Clercq (Brussels),(Brussels), Eric HautbrugeEric Hautbruge(Gembloux),(Gembloux), Regi Dedeken Regi Dedeken (Antwerp),(Antwerp), Dirk Berkvens Dirk Berkvens (Antwerp),(Antwerp),Stephan Zientara Stephan Zientara (Paris)(Paris)

�� The ABCD Team (European Advisory Board on Cat Diseases)The ABCD Team (European Advisory Board on Cat Diseases)chaired by Marian Horzinek:chaired by Marian Horzinek:

ACKNOWLEDGEMENTS

www.abcd-vets.org

Equine herpesviruses (EHV): from EHV-1 to EHV-5 … herpesvirus 4 Equine rhinopneumonitis (Equine...

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