herpesvirales & Poxviridae

• largest virus in veterinary field

• isolated from nearly all animal species

• 120-200nm

• aujekzy’s disease

• bovine herpesvirus type 1 infection

• equine rhinopneumontis

• koi herpesvirus infection of crap, infectious laryngotracheitis of poultra, marek disease

• once infected with HV, always infected

characteristic morphology under EM -> round form in cell -> spiegelei (gelb)

Core with genom in the capsid (icosaedral-100nm, 162 capsomers) covered by tegument (forms visible form ofHPV Partcile) coverd by envelope (contains lipids with projections (spikes)

outer envelope: glycoproteins (named from A,B,C,.. depending pn virus)

outer tegument and inner tegument: specific for HV (function for replikation cycle: proteins help to start)

Major capsid protein

Nucelocapsid witg triplex and portal vertex

tegument - help with replication - mainly non-structure protens

• linear genome - 2 strands are linear to each other

• circular version in nucleus - can covalently bind => circled version (episom)

• inverted repeat regions (enable circulation)

• DNA replication “rolling circle” -> based on circles version of the genome

• inverted repeat: possible to switch from linear to circular. ligase will ligase them to covalent linked ones

• I————————IIIIII——IIIIII

  UL (unique long). Us

• IIIIII——————————IIIIII

  inverted repeat region -> repeated in the genome there they can bind to each other -> covalent => circle version of genome

• genetical complex:

  • essentielle genes: genome replication, entry-assembly-release (infection life cycle immune invasion genes)

  • non-essentielle genes: influence on cell and host defense. Encode for proteins which have an impact in host immune system. most target innate immune system

• cascading - regulated in timley

  • 1 immediate-early genes - encode for non.ess. genes/mainly kind of immune invasion genes, aim =inhibit immune system

  • 2 delayed-early genes - replication cycle

  • 3 late genes - encode for structural proteins

many factors to inhibit host immune sytsem -> all kind of innate immune sytem

e.g. T-cell - TCR, neutrophil - chemokine receptor

infection:

• adsorption

• penetration

• uncoating

• virus tegument binds to specific receptor on cell membrane - viraö capsid release in cell and transported via microtubuli to the nucleus -> via nuclear pores the viral DNA goes into the nucleus -> viral genome circular (episome) -> replication and many viral genes produced. -> circular DNA has no free ways were DNAse could act on -> aim to avoid degradation -> viral genomes out over golgi, glycoprotein is waiting there to form a Tegument. releases via trans goli network

• imidietly with adsorption-> uncoating, only capsid in the cell. proteins mediate, that the capsid is transfeered to the nucleus-trough microtuble

morphogenesis: newly synthesized viral particles released - assembly/maturation/release

the herpes virus genom is circular in the nucleus

specific origins of replication -> production of 3’ and 5’end. from 5’ -> 3’

5’ produces okazaki fragment.

endonuclease on nick -> ssDNA binding protein and polymerase and DNA gyrase binding on nick/endonuclease -> RNA primase on polymerase -> reading of DNA -> linear genomic concatemers produces. cut and packed via capsid

Fork replikation -> dsDNA opend and rolling circle on one ssDNA

• delayed infection

• after initil infection -> virus is there for ever maybe.

• Infection, which persists for a long period (eg. HIV, Ebola) after primary infection

• existing biological balance, so infected cells/the host usually wont be damaged

• formation and excretion of infectious viruses

HPV - can switch from sleeping mode to active mode

• presence of virus is restricted to DNA - or parts of it - and eventually of single viral proteins

• no synthesis of infectious virus

• a latent infection can be activated to a persistent or acute infection

episome maintains in genome

• primary infection with productive cycle

• no full clearance of virus

• in certain cells genome is latently present = no infectious virus

• extreme restrict gene expression : LAT- latency associated transcriptome -> when reproduction is done

• reactivation possibly during stress etc

• all herpes viruses can establish a latent infection in their natural host

• effect on everything= epidemiological super strategy

3 families:

1. herpesviridae -subfam/ genera

2. alloherpesviridae - genera

3. maloceherpesviridae - genera

structured on the basis - biological characteristic/ Molecular data/ DNA sequence information

• variable host spectrum

• relativley short replication cycle and fast spreading in the cell culture

• efficient destruction of infected cells -> in the end

• ability to establish a latent infection in (mainly) neurons, sensoric NS

• genetic, genome assembly

• Genus:

  • simplexvirus

  • variocellovirus

• narrow host spectrum - mostly humand

• long replication cycle

• slow proceeding of infection in cell culture

• infected cells often enlarged (Cytomegaly)

• latent in monocytic cells

• genetic

• genus

  • cytomegalovirus: Human HV5 HCMV

  • muromegalovirus

  • proboscivirus

  • roselovirus (Humanes HV6)

• specific host spectrum

• specific fot T- or B-lymphocyzes, often infection without production of infectious progen virus

• latent frequent in lymphatic tissue (infection)

• genus:

  • lymphocryptovirus (HHV4 - Epstein barr virus)

  • Rhadinovirus

  • Macavirus (AlcelaphinesHV1)

  • percavirus (Equid HV2)

Rhinopneumonitis/viral abortation of mares (in pregnant horses)

EHV4 maybe respiratory form of EHV1

• subfamily: Alphaherpesvirinae

  • genus: variocellovirus

• OIE-listed disease

• EHV1 and EHV4 immunological closley related virus, which are 55-84% genomical identical

• lifelong latency

• highly contagious disease

• transmission through direct contaact after extreaction via mucosa, especially respiratory mucosa in case of abortion via amniotic fluid, fetus, placenta; indirect

• clinically inapparent animals

• morbidity: up to 100%, lethality low

• infection through direct contact oronasal admission

• primary reproduction in respiratory epithelia

• lymphocyte-associated viraemie EHV-1, systemic spreading EHV1

• secundary target organs: uterus CNS

1. new viruses produced and infection in horses on respiratory epithelium

2. lamina propria -> leucocytes in -> blood/lymphatic vessel

3. blood and/or lymphatic circulation => utero-placenal interface - blood vessels of uterus and placenta gets destroid

• infection of progeny via migrating lymphocytes and infection of endothelia of umbilical artery

• vessels CNS

• large enveloped dsDNA viruses, genome 130-370kb

• compley strucutre, coboidal to oval

• particle size 300x240x150nm

• encode 200proteins <60 regulatory proteins

EV envelope and MV membrane = both enveloped - mature virion with membrane and enveloped virion with virion

lateral body

core wall

nucleocapsid

difference - process of getting out of the cell

circular - connection between the 2 genomes

structure of the genome of poxviruses - vaccinaviruses (s.33)

dsDNA - covalent linked ends

inverted sequences on the ends of the genome ITR

Replication exclusivley within the cytoplasm!

-> dont need connection to nucleus /cell machinery =reasone for big genome

• entry into the cell: via fusion or endocytosis -> absolut independet of cell machinery (e virus proteins for attachement, 11 virusproteins for fusion -> receptor mediated endocytosis

• virus-originated enzymes e.g. for transcrition and DNA-replication

• cascade-like regulation of the early intermediate and late transcription:

  • early still virion (packaged)

  • intermediate with DNA replication

  • laze after DNA replication (strucutral proteins being produced)

• genexpression independet from functions of the nucleus (e.g. no splicing)

• formation of virus factories

• early and late proteins for morphogenesis

• ER membrane remodeled for first envelope, further enveloped in double membrane of cell-trans-golgi-network

• 3 forms of infectious particles

  • intercellular- 1 envelope

  • intracellular - 3 envelopes

  • extracelular - 2 envelopes

  • virions

• release by lysis (intracellular) or fusion of outer membrane with cell membrane (extracellular)

• local or generalized infections (skin tropism)

• induction of postular or proliferative lesions

• capacity for immune evasion (innate - adapive responses)

• serological cross-reactivity within a genus

• high tenacity in the dried state

systemic infections with high morbidity and mortality

• variolavirus => human

• extromeliavirus => mouse

• camelpoxvirus => dromedarary camels (no zoonosis)

first infectious diease eradicated worldwide

-> no animal reservoir

• prototype of a live vaccine, origin unknown

• “classical” vaccine against human smallpox

• orthopox virus species with broas host range

• diseases in animals, “horsepox”, “rabbitpox”, “buffalopox”

• cattle in india, brazilm argentina; natural reservoirs?

• use as vector for expression of heterologous proteins recombinant vaccines - abschaben von infizierter haut um vaccine zu erstellen

OPV Eurasiens

Zoonosis!

• broas host range in mammaly-> big cats (leopard, puma, jaguar…) Elephant, rat, cat, human

• reservoir in rodents?

• cattle historically, humans cats and zoo animals are end links of an infectiozs chain

• mostly local infections, gneralization in case of immunosuppression

report necessary bc of zoonosis

• reservoir in rodents

• broad host spectrum: maraque-monkeys; human also generalizing infections

• viral strains with different virulenc

• 37 laboratory confirmed cases

• transmission linked to ill prairie dogs

• no human to human spres observed in absence of an infected animal

• disease mostly mild

• clinical features: rash, fever, respiratory disease, lymphadenopathy

pathogen detection on skin lesions, crusts vesicular fluid, organs witg:

EM - fast, sensitie, diagnosis just “orthopox-like” viruses

PCR - highly sensitive, highly specific

cultivation in cell culture (rar chicken egg -CAM)

ELISA and IF - uses less frequently

AK detection with ELISA, neutralization (PRNT)

Goatpox viurs, sheeppox virus

report necessary

• fever, edema, resp. symptoms

• nodules and necroses in the skin, formation of crusts and scares

• ulcerations in the mouth area promote virus spreading

• up to 75% in the herd affected

• mortality 5-10% young animals and imports up to 100%

diagnosis via EM with clinical picture

bovine north africa, near east

• fever, generalized changes of the skin

• morbidity up to 85%, mortality variable

• report necessary

• morbidity in cattle herds 0-95%

• incubatuon period 5-10d

• erythema at the site of entry

• -> hemorrhagic tumor & generalisation

• conjunctivitis, fever, disturbances of general condition, swelling of the (mucous) skin (“lions’s head”)

• much milder course in endemic areas

• virulence of the pathogen

• resistance of the population

Diagnosis

• clinics

• detection of pathogen : EM

• AB detection

prophylaxis

• live vaccines (mandatory reporting)

worldwide distribution, sporadic occurrence

mortality in piglets up to 30%; usually milder course in adult pigs

wall-like skin changes, especially on the underside of the abdomen, ears

transmission by stining insects (pig lice)