Family: Herpesviridae, Subfamily: Alphaherpesvirinae Flashcards
Virus morphology for family Herpesviridae
Eneveloped, spherical
Icosahedral capsid, T=16
Capsid consists of 162 capsomeres and is surrounded by a layer of globular material, known as tegument
Viral genome for family Herpesviridae
Monopartite (non-segmented), linear, double-stranded DNA genome
Herpesvirus genes fall into 3 categories
- those encoding proteins concerned with regulatory functions and virus replication (immediate early and early gnees)
- those encoding structural proteins (late genes)
- a heterologous set of “optional” genes; they are not found in all herpesviruses and are not required for replication
Viral replication of family Herpesviridae
DNA replication and encapsidation occur in the nucleus
Viral envelope is acquired by budding through the inner layer of the nuclear envelope (instead of cytoplasmic membrane like other viruses)
Mature virions accumulate within vacuoles in the cytoplasm and are released by exocytosis or cytolysis
Infection with Herpesviruses
Persistent infection with periodic or continuous shedding occurs in all herpesvirus infections
Sheddig of virus in nasal, oral, or genital secretions provides the source of infection for others
reactivation of latent herpesvirus infection is associated with stress
Inclusion bodies of Herpesviruses
Eosinophilic intranuclear inclusion bodies
Known as Type A Cowdry bodies
Inclusion bodies are composed of nucleic acid and protein
Bovine Herpesvirus 1 etiology
Only one serotype of BHV-1 is recognized 3 subtypes of BHV-1: BHV-1.1 = respiratory subtype BHV-1.2 = genital subtype BHV-1.3 = encephalitic subtype
Transmission of Bovine Herpesvirus 1
Respiratory disease and conjunctivitis result from droplet transmission
Genital disease may result from coitus or artificial insemination with infective semen
Pathogenesis of Bovine Herpesvirus 1
Dissemination from the initial focus of infection occurs via cell-associated viremia
In both genital and respiratory forms, the lesions are focal areas of epithelial cell necrosis in which there is ballooning of epithelial cells
Sites of Latency of Bovine Herpesvirus 1
Life-long infection with periodic shedding, source of new outbreaks
All seropositive animals are considered carriers
Trigeminal nerve = respiratory disease
Sciatic nerve = genital disease
Clinical signs of respiratory form of Bovine Herpesvirus 1
Red nose, Necrotic Rhinitis, Dust pneumonia
Inflamed nares give the appearance of having a “red nose” due to hyperemia
Nasal discharge becomes profuse and mucopurulent
Clinical signs of ocular form of IBR
Conjunctivitis is a common finding in “red nose”
Profuse ocular discharge
Do not misdiagnose as Pink Eye (Moraxella bovis) - IBR lesions are confined to the conjunctiva and no lesions on cornea except diffuse edema
Genital disease form of Bovine Herpesvirus 1
Infectious Pustular Vaginitis (IPV)
Frequent urination
Tail held in an elevated position and excessive tail switching
Balanoposthitis - inflammation and pustules in the mucosa of the penis and prepuce
Bovine Herpesvirus 2
Bovine ulcerative mammilitis
Direct contact and fomite mediate, through trauma to skin
Mechanical transmission by stable flies and other arthropods
Teat is swollen and painful, bluish skin, exudes serum, raw ulcers
High incidence of mastitis (reduction in milk yield)
Bovine Herpesvirus 2
Pseudo-lumpy Skin Disease
Mechanicla transmission by arthropods
Mild fever, followed by sudden appearance of skin nodules on the face, neck, back, and perineum
Shorter course of disease than Lumpy-skin diseae
Porcine Herpesvirus 1 common names
Pseudorabies
Aujeszky disease, Mad itch
Transmission of Porcine Herpesvirus 1 in primary host
Recovered pigs act as primary reservoirs and are latent carriers of the virus
Virus shed in saliva, nasal discharges, and milk of infected pigs
Transmission can occur by licking, biting, aerosol, ingestion of contaminated carcass, water, and feed
Transmission of Porcine Herpesvirus 1 in secondary host
Dogs and Cats = ingestion of infected pig carcass/meat, or rodents
Cattle = direct contact with infected pigs oral and nasal routes
Pathogenesis of Porcine Herpesvirus 1
Primary site of viral replication is the upper respiratory tract
Virus replicates in tonsils and nasopharynx
Brief viremia with virulent strains, with localization of virus in organs
Pathogenesis of Porcine Herpesvirus 1 in the CNS
Virus spreads to CNS via axons of cranial nerves with preference for neurons of the pons and medulla
CNS lesions - ganglioneuritis, nonsuppurative meningoencephalis, perivascular cuffing
Clinical signs of Porcine Herpesvirus 1
-sow, piglets, fattening pigs
Sows - poor fertility, abortion, stillbirth mummies, weak piglets, failure to farrow
Piglets - nervous signs, death
Fattening pigs - retarded growth
Clinical signs depending on age of Porcine Herpesvirus 1
Nonimmune piglets = 100% mortality
Nonimmune pregnant sows = 50% abortion rate
Older piglets, growers, and adults pigs = mild disease
A generalized febrile response, anorexia, and weight loss in infected pigs of all ages
Piglets born to nonimmune sows with Porcine Herpesvirus 1
Most susceptible
CNS disease signs - incoordination of hindlimbs, fitting, tremors, and paddling
Weaned pigs and growing pigs with Porcine Herpesvirus 1
CNS signs may be reduced and an increased in respiratory signs
Listlessness, depression, sneezing, coughing, fever, vomiting
Incoordination and pronounced muscle spasm
Nonimmune pregnant sows with Porcine Herpesvirus 1
Infection before 30th day of gestation = death and resorption of embryo
Infection in late pregnancy = mummified, macerated, stillborn, weak, or normal swine
Sows can be infertile on next breeding, but eventually conceive
Pseudorabies in secondary hosts
Cattle
Dogs
Cats
Pseudorabies in Cattle
Maditche intense pruritis cattle may become frenzied progressive involvement of CNS, paralyssi, ataxia death from respiratory failure
Pseudorabies in Dogs
frenzy associated with pruritis, self-mutilation
paralysis of jaws and pharynx with drooling of saliva
plaintive howling
unlike rabies, dogs do not tend to attack
Pseudorabies in Cats
disease progresses so rapidly that pruritis may not be observed
Vaccination for Porcine Herpesvirus 1
Do not prevent infection, but can alleviate clinical signs
Transmission of Equine Herpesvirus 1
Inhalation of infected aerosols, direct or indirect contact with nasal discharges, aborted fetuses, placenta, or placental fluids
Latent EHV-1
Latency of EHV-1 allows the virus to survive and spread
Latent EHV-1 can reside in tissues of the CNS (trigeminal ganglia) and lymph system without causing any clinical symptoms
Pathogenesis of EHV-1
Principal route of EHV-1 transmission is the respiratory tract
Virus infected mononuclear cells and T lymphocytes are released into circulation causing viremia
Reactivation results in shedding of virus from nasal epithelium and uterine infection
Cell-associated viremia confers protection from the body’s immune defenses and allows the virus to spread to endothelial cells lining blood vessels in the CNS and pregnant uterus, resulting in CNS signs or abortion
Central lesion caused by EHV-1
An infection of endothelial cells, leading to vascular necrosis, thrombus formation and death to the tissues serviced by these blood vessels (ischemia) is responsible for the three types of conditions seen - respiratory, reproductive, and CNS
Immunosuppression of EHV-1
EHV-1 codes a protein that inhibits TAP protein, thereby blocking delivery of antigen to class 1 MHC molecules
3 types of conditons of EHV-1
Respiratory disease
Encephalomyelopathy
Reproductive form
Respiratorydisease of EHV-1
Mostly younger horses
Rhinopneumonitis
Fever, bilateral nasal discharge, coughing, inappetence, and depression
Encephalomyelopathy (EHM) of EHV-1
Horses of any age or breed
Characterized by immune-mediated vasculitis leading to infarction and hemorrhage within brain and spinal cord
Range from hindlimb incoordinatiion to quadriplegia and recumbency resulting in death
Reproductive form of EHV-1
Majority of abortions occur in the last trimester
Reproductive efficiency is not compromised
If susceptible mares are exposed to the aborted conceptus the abortion outbreaks can
Natural immunity to EHV-1 about 2-3 years, thus abortion storms are in 3 year cycles
Transmission of EHV-4
Sporadic infections
Mostly in horses under 2 years of age
Causes a lifelong latent infection
Droplet infection from infected horses and older horses in which viral shedding occurs
Pathogenesis of EHV-4
Less severe tissue destruction
Rarely causes abortion
Rarely results in viremia
Rarely results in death
Clinical signs of EHV-4
Upper respiratory tract diseae (rhinopharyngitis and tracheobronchitis)
Nasal discharge that may progress into a mucoid or mucopurulent discharge, increased lung sounds, mild coughing, fever
Vaccination of EHV-4
Ideal vaccine prevents early infection of suckling foals as well as latency of infection in pregnant mares
Infected mare passes EHV-4 to foal = target for vaccination to limit viral infection of foal from shedding by infected mares
Infected foal sheds the virus acting as a source of infection for other pregnant mares = target for vaccination limiting transmission from infected foals to pregnant mares
Common name of Canine Herpesvirus 1
Hemorrhagic disease of puppies
Fading puppy syndrome
CHV-1 Transmission
Neonates - contact with infected oral, nasal, or vaginal secretions of dam; in-utero transmission; from passage through birth canal; contact with secretions of littermates
Older dogs - veneral transmission; contact with saliva, nasal discharge, or urine
In-utero infection pathogenesis of CHV-1
Abortion, stillbirth, infertility
If the pup survives, it will most likely develop systemic CHV-1 infections
Systemic neonatal infection pathogenesis of CHV-1
Initial replication in nasal epithelium, tonsils, and pharynx
Mucosal invasion is followed by leukocyte (macrophage)-associated viremia
Diffuse necrotizing vasculitis, multiple hemorrhagic necrosis in organs
Thrombocytopenia, DIC
CNS infection pathogenesis of CHV-1
Meningoencephalitis occurs in oro-nasally infected neonatal puppies
Virus may travel up nerve axons to CNS
Puppies die from systemic infection before neurologic signs are seen
Factors governing systemic neonatal infection of CHV-1
- Body temperature of puppies:
CHV-1 replicates at 33 C, the temperature of the outer genital and upper respiratory tracts
the more sever the hypothermia, the more severe and rapid the course of disease - Maternal immunity:
maternal Abs provide protection
pups born from seronegative bitches are highly vulnerable to severe disease
Clinical signs of CHV-1 in puppies
Painful crying, abdominal pain, anorexia, dyspnea
Passing soft, odorless, greenish stool
No elevation in body temperature
Those that survive systemic disease develop persistent neurologic signs, such as ataxia, blindness
Pathogenesis of CHV-1 in adults
- Genital infections
Female: asymptomatic; vesicular vaginitis with discharges; abortion, stillorn, mummified fetuses
Male: balanoposthitis - Respiratory infections (rhinitis and pharyngitis)
- Ocular infection (conjunctivitis)
Control of CHV-1
Reduce hypothermia by providing heated whelping boxes, or placing puppies under an infrared lamp
Isolated of infected bitch and her litter
Low prevalence of severe illness in pups and paucity of clinical signs in adult animals has resulted in lack of availability of vaccines
Feline herpesvirus 1 commone name and common cause of….
Feline Rhinotracheitis
One of the two most common causes of infectious respiratory diseases in cats, the other is feline calicivirus (FCV)
Transmission of FHV-1
Shed primarily in ocular, nasal, and oral secretions
Spread largely by direct contact with an infected cat
All recovered cats become latently infected carriers
Pathogenesis of FHV-1
Virus replication takes place in the mucosae of nasal septum, tubinates, nasopharynx, and tonsils
Viremia is rare as virus replication is restricted to areas of low temperature, upper respiratory tract
Clinical signs of FHV-1 in kittens
Sever upper respiratory disease
Extensive rhinotracheitis
Fatal bronchopneumonia (from secondary bacterial infection)
Conjunctivitis and ulcerative keratitis
Clinical signs of FHV-1 in pregnant queens
Abortion around 6th week of pregnancy
No evidence that virus crosses the placenta
May be due to severe systemic effects of illness, and not direct effect of virus
Diagnosis of FHV-1
Detection of corneal ulcers using Fluorescin Ophthalmic Strips
An intact corneal epithelium has a high lipid contect that resists the penetration of fluorescein and so is not colored by it
A break in corneal epithelium allows water-soluble fluorescein to be absorbed by the hydrophilic corneal stroma
Vaccinations for FHV-1
3 types of FHV-1 and FCV vaccines are avaiable:
Modified live virus (MLV) parenterally
MLV intranasally
Inactivated vaccine parenterally
Gallid Herpesvirus 1 common name and host
Infectious Laryngotracheitis
Highly contagious infection of chickens
Transmission of GHV-1
Mostly by inhalation
Droplets to conjunctiva
Recovered and vaccinated chickens can serve as carriers
Mechanical transmission through scavengers like vultures, crows, domestic dogs
Pathogenesis of GHV-1
Severe laryngotracheitis in affected birds, characteried by necrosis, hemorrhage, ulceration, and the formation of diphtheritic membranes
Diphtheritic membrane formation can form a second tube in the trachea, blocking air passage, result in death from asphyxia
Trigeminal ganglion is target for viral latency
Clinical signs of severe form of GHV-1
Respiratory distress, head shaking and coughing
Neck is raised and head is extended during inspiration -> pump handle respiration
Cough can result in explosion of bloody mucous
Clinical signs of less virulent GHV-1
Low virulent strains are associated with conjunctivitis, ocular discharge, swollen infraorbital and nasal sinuses, and decreased egg production
Clinical signs of mild enzootic form of GHV-1
The mild enzootic form is the most common in modern poultry production
Severe epizootic form is uncommon
Diagnosis of GHV-1
Necropsy findings - tracheal plug (diphtheric membrane)
Vaccination of GHV-1
- Chick embryo origin (CEO) - vaccines have the capability of reverting to virulence and causing ILT signs; induce better immunity
- Tissue culture origin (TCO) - vaccines are given by eye drop and does not spread or revert to virulence; level of induced immunity is limited
- A pox-vectored recombinant vaccine
Gallid Herpesvirus 2 common name and hosts
Marek’s Disease
Very important disease of poultry
Chickens are the most important natural host
Transmission of GHV-2
Inhalation of infectious feather debris, chicken dander, or dust
Cell free viruses release from feather follicles are highly infectious, but labile
Viruses in desquamated cells (dander) are less infectious, but can survive in poultry house dust or litter
4 pathotypes of GHV-2
- Mild (mMDV) - neural MD; preventable with HVT (turkey herpesvirus vaccine)
- Virulent (vMDV) - neural and visceral lymphomas; preventable with HVT
- Very virulent (vvMDV) - neural and visceral lymphomas; oncogenic in HVT vaccinated chickens; preventable with bivalent vaccines
- Very virulent plus (vv+MDV) - neural and visceral lymphomas; oncogenic in chickens vaccinated with bivalent vaccines
Pathogenesis of fully productive infection of GHV-2
Production of enveloped virions and cell death (lysis)
Occurs only in feather follicle epithelium
Infected T cells are the ‘Trojan Horse’ by which MDV enters the feather follicle epithelium
Pathogenesis of productive-restrictive infection of GHV-2
Production of naked virions (not infectious) and viral antigens
Cell death (lysis)
Occurs in B ells and activated T cells
Profound immunosuppression
Pathogenesis of non-productive infection of GHV-2
Viral genome persists in T cells
No antigens expressed
Pathogenesis of non-productive neoplastic transformation of GHV-2
Latently infected T cells undergo neoplastic transformation
New antigen, MATSA (Marek’s diseae associated tumor specific antigen), appears in transformed T cells
Genetic susceptibility of GHV-2
Susceptibility varies depending on different MHC II halotypes
B19 halotype chickens are highly susceptible to MD
B21 halotype chickens are genetically resistant to MD
Neuolymphomatosis of GHV-2
Enlargement of nerve trunks
Peripheral nerves become enlarged and lose their striations
Edematous, grey or yellowish appearance
Lameness, droopy wings ,paresis of legs (one leg forward and the other backward, limberneck, torticollis, incoordination
Visceral lymphomatosis of GHV-2
Diffuse or nodular lymphoid tumors in organs (liver, spleen, gonads, heart, lung, kidney, muscle, proventriculus)
Bursa is rarely tumerous and frequently atrophic
Absence fo bursal tumors helps distinguish the diseae from lymphoid leukosis
Ocular lymphomatosis of GHV-2
Graying of the iris
Interference with normal pupular constriction and dilation
Due to T cell infiltration
Partial or total blindness
Cutaneous lymphomatosis of GHV-2
Plucking of feathers reveal nodular lesions on skin
Enlarged feather follicles (skin leukosis)
Control of GHV-2
Reportable disease
Most widely used vaccine consists of turkey herpesvirus (HVT)
Bivalent vaccines consist of HVT and either SB-1 or 301B/1 strains of GHV-3
