Exam 2 - Family: Herpesviridae Flashcards
Herpesviridae Virus Morphology
- Enveloped, spherical to pleomorphic
- 150-200 nm in diameter
- Icosahedral capsid, T=16
- 162 capsomers surrounded by a layer known as tegument
- Glycoproteins embedded in lipid envelope
Herpesviridae Viral Genome
Monopartite (non-segmented), linear, double-stranded DNA genome. Fall in three categories.
Herpesviridae Viral Genome: Three Categories
- Those encoding proteins concerned with regulatory functions and virus replication
- Those encoding structural proteins
- A heterologous set of “optional” genes
Herpesviridae Viral Replication
- Occurs in the nucleus
- Viral envelope is acquired by budding and obtaining the nuclear envelope
- Mature virions are released by exocytosis or cytolysis
Herepesviridae General Charcteristics
- Do not survive well outside the host
- Requires close contact transmission
- Latently infected animals serve as a reservoir
- Can be oncogenic
- Reactivation of latent herpesvirus infection is usually associated with stress and glucocorticoid drugs
- Characteristic eosinophilic intranuclear inclusion bodies
- Cell-to-cell fusion facilitates spread of infection and virus
Herpresviridae Inclusion Bodies
Type A Cowdry bodies. Composed of nucleic acid and protein.
Subfamily: Alphaherpesvirinae
This includes:
- Bovine herpesvirus-1
- Bovine herpesvirus-2
- Equine herpesvirus-1
- Equine herpesvirus-4
- Porcine herpesvirus-1
- Feline herpesvirus-1
- Canine herpesvirus-1
- Gallid herpesvirus-1
- Gallid herpesvirus-2
Alphasherpesvirinae Properties
Highly cytopathic, lyse infected cells. Short replication cycle. Episomes are integrated into the chromosomal DNA of latently infected neurons. Produce localized lesions in the skin and mucosae of respiratory and genital tract. Pregnant animals - abortion characteristically with multifocal areas of necrosis in several fetal organs.
Bovine herpesvirus-1 (BHV-1) Diseases
Infectious bovine rhinotracheitis (IBR), pustular vulvovaginitis. Balanoposthitis, conjunctivitis, abortion, enteritis, and generalized disease of newborn calves.
BHV-1 serotype and subtype
Only a single serotype of BHV-1 is recognized
3 subtypes:
- BHV-1.1 = respiratory subtype
- BHV-1.2 = genital subtype
- BHV-1.3 = encephalitic subtype
BHV-1 Transmission
Droplet transmission and either coitus or artificial insemination
BHV-1 Pathogenesis
In both genital and respiratory form of the disease, the lesions are focal areas of epithelial cell necrosis in which there is ballooning of epithelial cells.
Intense inflammatory response within the necrotic mucosa, frequently with formation of an overlying accumulation of fibrin and cellular debris (pseudomembrane).
Site of Latency - Trigeminal Nerve
Respiratory disease with BHV-1
Site of Latency - Sciatic Nerve
Genital disease with BHV-1
BHV-1 Clinical signs - Respiratory form
Red nose, Necrotic rhinitis, dust pneumonia
BHV-1 Clinical signs - Ocular form of IBR
Conjunctivitis is a common finding with “red nose”
DO NOT misdiagnose as pink eye. IBR lesions are confined to the conjunctiva and no lesions on cornea except diffuse edema.
BHV-1 Abortion
Can result from MLV vaccines given to pregnant animals. Higher incidences with fetuses infected in the second half of gestation.
BHV-1 Systemic Disease of Newborn Calves
Typically less than 10 days. Calves develop a generalized disease with pyrexia, diarrhea, respiratory distress, ocular discharge, incoordination, eventually convulsion and death.
BHV-1 Genital Disease - IPV`
Infectious Pustular Vaginitis. Vaginal discharge, vulva swollen, red spots, and discrete pustules
BHV-1 Genital Disease - Balanoposthitis
Inflammation and pustules in the mucosa of the penis and prepuce
BHV-1 Control (Vaccination)
MLV, subunit and inactivated vaccines. Subunit vaccines contain the major surface glycoproteins that elicit antibody response.
Bovine herpesvirus-2 (BHV-2)
Causes bovine ulcerative mammillitis and Pseudo Lumpy Skin Disease
Bovine ulcerative mammillitis - Host
Cattle, heifers, usualy within 2 weeks after calving
Bovine ulcerative mammillitis - Transmission
Direct contact and mechanical transmission
Bovine ulcerative mammillitis - Clinical signs
Swollen, painful teat. Skin is bluish, exudes serum, formation of raw ulcers.
Pseudo Lumpy Skin Disease - Distribution
Southern Africa
Pseudo Lumpy Skin Disease - Transmission
Mechanical Transmission
Pseudo Lumpy Skin Disease - Clinical Signs
Sudden appearance of skin nodules. Nodules are flat with slightly depressed center and can undergo necrosis.
Porcine herpesvirus-1/ Suidherpesvirus-1
Causes Pseudorabies (Aujesky disease, Mad itch)
Pseudorabies - Hosts
Primary host: Pigs
Secondary host: horses, cattle, sheep, goats, dogs, cats, etc.
Pseudorabies - Transmission Primary Host
Typically are reservoirs from pigs and rodents that are latent carriers shedding the virus. Can be be through saliva, nasal discharges and milk.
VIRUS DOES NOT SHED IN URINE OR FECES.
Pseudorabies - Transmission Secondary Host
Dogs & Cats - ingestion of infected pig meat or rodents
Cattle - direct contact with pigs
Pseudorabies - Pathogenesis
Primary site of viral replication is upper respiratory tract.
Pseudorabies - Spread of Virus
Via the lymphatics to regional lymph nodes, where replication continues
Pseudorabies - Spread of Virus CNS
Spread to CNS via axons of cranial nerves. Preference for neurons of the pons and medulla.
Pseudorabies - CNS Lesions
Ganglioneuritis, non-suppurative meningoencephalitis, perivascular cuffing
Pseudorabies - Clinical signs
Depend on the age of the affected pig.
Pruritus, a dominant feature in secondary hosts, is rare in pigs.
Pseudorabies - Necropsy Findings
Gross lesions are often absent or minimal. Liver and spleen have yellow-white necrotic foci.
Pseudorabies - Cattle (Mad Itch)
Intense pruritus, frenzied, progressive CNS involvement, stage or paralysis, ataxia, death from respiratory failure, self trauma, profuse salivation.
Pseudorabies - Dogs
Frenzy, pruritis, self mutilation, paralysis of jaw and pharynx, drooling, plaintive howling. THEY DO NOT ATTACK.
Pseudorabies - Cats
Disease progress so rapidly that pruritus may not be observed
Pseudorabies - Diagnosis
History and clinical signs. Histopathology - intranuclear eosinophilic inclusion bodies. PCR, ELISA.
Pseudorabies - Vaccination In Pigs
In enzootic areas. Recombinant DNA deletion mutant, live-attenuated and inactivated vaccines available. DO NOT PREVENT INFECTION, but cal alleviate clinical signs in pigs.
(def. Enzootic: relating to, or denoting a disease that regularly affects animals in a particular district or at a particular season.)
Equine herpesvirus-1 (EHV-1)
Most virulent equine herpesvirus.
EHV-1 Transmission
Inhalation of infected aerosols, direct or indirect contact with nasal discharges, aborted fetuses, placenta or placenta fluids.
EHV-1 - Latency
Maintains the virus. Can reside in tissues of CNS specifically the trigeminal nerve. Can also reside in lymph system (specifically lymphocyte).
EHV-1 Pathogenesis
Cell-associated viremia. Principal route is through the respiratory tract. Infects endothelial cells in lamina propria.
The central lesion caused by EHV-1 responsible for the three types of conditions seen (respiratory, reproductive & CNS).
EHV-1 Immunosuppression
Codes a protein that inhibits TAP protein, thereby blocking delivery of antigen to class I MHC molecules.
EHV-1 Respiratory Disease
Affect mostly younger horses. Rhinopneumonitis. Fever, bilateral nasal discharge, coughing, inappetence, and depression.
EHV-1 Encephalomyelopathy
EHM, Equine Herpesvirus Myeloencephalopathy
Characterized by immune mediated vasculitis leading to infarction and hemorrhage within the brain and spinal cord.
EHV-1 Reproductive Form
Abortions can occurs between 8-10 months of gestation. Reproductive efficiency is not compromised.
Equine Herpesvirus-4
Equine Viral Rhinopneumonitis
EHV-4 - Transmission
Observed in horses under two years of age, causes life long latent infection. Droplet infection from infected horses and older horses in which inapparent viral shedding occurs.
EHV-4 Pathogenesis
Causes less severe tissue destruction than EHV-1. Rarely causes abortions and rarely results in viremia. Death is rare.
EHV-4 Clinical signs
Results primarily in upper respiratory tract disase (rhinoparhyngitis and tracheobronchitis). Also include nasal discharge, mild coughing, fever and lung sounds.
EHV-4 Vaccination
Live attenuated and inactivated commercial EHV-1 vaccines are available, including combined products that include both EHV-1 and EHV-4
Canine Herpesvirus -1 (CHV-1)
Hemorrhagic disease of puppies (fading puppy syndrome)
CHV-1 Transmission - Neonates
Contact with infected oral, nasal or vaginal secretion of dam. In-utero transmission.
CHV-1 Transmission - Older dogs
Venereal transmission. Contact with saliva, nasal discharge, or urine of infected dogs or puppies.
CHV-1 Pathogenesis - In-utero
Abortion, stillbirth, infertility. Most pups develop systemic infection within 9 days from birth.
CHV-1 Pathogenesis - Systemic Neonatal Infection
Less than 1 week. Replication occurs in nasal epithelium, tonsils and pharynx. Leukocyte associated viremia. Virus replication in endothelial cells. Diffuse necrotizing vasculitis, multiple hemorrhagic necrosis in several organs.
CHV-1 Pathogenesis - CNS infection
Meningoencephalitis commonly occurs in oro-nasally infected neonatal puppies.
CHV-1 Factors governing systemic neonatal infection
Body temperature & Maternal immunity.
Body temperature: CHV-1 replicates optimally at 33oC (the temperature of upper respiratory and genital tracts.) If pups aren’t warm enough they can be more susceptible to this disease.
CHV-1 Clinical signs in puppies
Painful crying, abdominal pain, anorexia, dyspnea, passing soft odorless, greenish stool, no elevation in body temperature. Persistent neurological signs such as ataxia and blindness.
CHV-1 Adult female genital infection
Generally asymptomatic or limited vaginal hyperemia. Vesicular vaginitis with discharges. In-utero infections.
CHV-1 Adult male genital infection
Balanoposthitis
CHV-1 Clinical signs in adults
respiratory infections and ocular infections
CHV-1 Diagnosis
Focal area of necrosis and hemorrhages in multiple organs. Intranuclear inclusion bodies may be present. Causative virus can be isolated readily in canine cell cultures. Nucleic acid detection.
CHV-1 Control
Keeping puppies in warm temperature. Isolation of infected mother and pups. Lack of available vaccines.
Feline Herpesvirus-1
Causes feline rhinotracheitis
FHV-1 Transmission
Spread is largely by direct contact with an infected cat OR by aerosol route (not considered important).
FHV-1 Pathogenesis
Replication takes place in mucosae of nasal septum, turbinates, nasopharynx and tonsils. Restricted to low temperature (upper respiratory tract)
FHV-1 Clinical signs - Kitten
up to 4 weeks. Severe upper respiratory disease. Extensive rhinotracheitis. Fatal bronchopneumonia may develop. Conjunctivitis and ulcerative keratitis.
FHV-1 Clinical signs - Cats
> 6 months; mild or subclinical disease in older kittens
FHV-1 Clinical signs - Pregnant Queen
Abortion around 6th week of pregnancy. No evidence that the virus crosses the placenta. Conjunctivitis, hyperemia and serous ocular discharge, ulcerative keratitis.
FHV-1 - Diagnostics - Ophthalmic strips
Detection of corneal ulcers using Fluorescein. A break in the corneal epithelium allows water-soluble fluorescein to be absorbed by the hydrophilic corneal stroma. The exposed, and now stained, corneal stroma will therefore fluoresce.
How to differentiate FHV-1 with Feline Calicivirus (FCV) infection
Ulcers on tongue of cat are common with FCV. Oral ulcers are rare in cats with FHV-1 infection.
FHV-1 Diagnosis
Histopathology: lesions include necrosis of epithelia of nasal cavity, pharynx, epiglottis, tonsils, larynx and trachea. Virus isolation with ocular or pharyngeal swab. Serology.
FHV-1 Vaccination
MLV parenterally, MLV intranasally, and inactivated vaccine parenterally.
Gallid Herpesvirus-1
Infection Laryngotracheitis (ILT)
Gallid Herpesvirus-2
Marek’s Disease
ILT- Host
Chickens, most common in ages 4-18 months. Also pheasants, partridges and peafowl
ILT-Transmission
Inhalation, droplets to conjunctiva, and occasionally ingestion. Mechanical transmission through scavengers.
ILT- Pathogenesis
Necrosis, hemorrhagic, ulceration and formation of the diphthertic membrane. Second tube formation, can block air passage. Trigeminal ganglion is the latency site.
ILT - Clinical signs
Mild coughing, sneezing followed by nasal and ocular discharge, dyspnea, loud gasping, coughing and depression.
ILT - Incubation period
6-12 days
ILT- Clinical signs - Severe form
Severe respiratory distress. Head shaking with coughing. Raised neck and head “pump handle respiration”. Cough of blood mucus.
ILT-Clinical signs - low virulence
Conjunctivitis, ocular discharge, swollen infraorbital and nasal sinuses, and decreased egg production.
ILT - Diagnosis
Tracheal plug, detection of typical intranuclear inclusions in respiratory tissues. Virus grows well in CAM of embryonated eggs.
ILT - Control
Complete depopulation and culling of infected birds and premises.
ILT- Vaccination - 3 types
- Chick Embryo Origin (CEO)
- Tissue Culture Origin (TCO)
- Pox vectors recombinant
CEO Vaccine
Vaccines have the capability of reverting to virulence and causing full blown ILT signs. Induce better immunity.
TCO
Vaccine is only given by eye drop and does not spread significantly or revert to virulence. Level of induced immunity is limited.
ILT vaccines can backfire
Veterinary vaccines have been found to combine into new infectious viruses.
Marek’s disease - Synonym
Fowl paralysis, range paralysis, polyneuritis, neurolymphomatosis.
Very important disease of poultry
Marek’s disease - Hosts
Chickens, turkeys, quails, pheasants
Marek’s disease - Transmission
Cell free viruses release from the feather follicles are highly infectious but labile. Viruses in desquamated cells (dander) are less infectious, but can survive in poultry house dust or litter for several months.
Marek’s disease - 4 Pathotypes
- mMDV
- vMDV
- vvMDV
- vv+MDV
mMDV
Mild Marek’s disease. Most associated with neural MD. Disease is preventable with HVT (Turkey’s herpesvirus vaccine
vMDV
Virulent Marek’s disease. Associated with high incidence of neural and visceral lymphomas. Disease is preventable with HVT (Turkey herpesvirus vaccine)
vvMDV
Very Virulent Marek’s disease. Associated with high incidence of neural and visceral lymphomas. Viruses are oncogenic in HVT vaccinated chickens. Disease preventable with bivalent vaccines.
vv+MDV
Very Virulent Plus Marek’s disease. Associated with high incidence of neural and visceral lymphomas. Viruses are oncogenic in chickens vaccinted with bivalent vaccines.
Marek’s disease - Pathogenesis
Various overlapping virus-cell interactions have been observed.
Marek’s disease - Fully productive infection
Production of enveloped virions and cell death (lysis). Occurs only in feather follicle epithelium. Infected T cells appear to be the “trojan horse” by which MDV enters the feather-follicle epithelium.
Marek’s disease - Productive-restrictive infection
Production of naked virions (not infectious) and viral antigens. Cell death due to lysis. Occurs in B-cells and activated T-cell (primarily CD4+ cells). Profound immunosuppression.
Marek’s disease - Non-productive infection
Viral genome persists in T-cells undergo neoplastic transformation. A new antigen, MATSA (Marek’s Disease Associated Tumor Specific Antigen), appears in transformed T-cells.
Marek’s Disease Virus is slowly cytopathic and remain associated with cells.
Cell free infectious viruses are almost impossible to obtain, except in dander from feather follicles. Lesions in Marek’s Disease result from infiltration and in situ proliferation of transformed T lymphocytes.
Marek’s disease - Genetic susceptibility
Varies depending on different MHC class II haplotypes
B19 haplotype
Chickens are highly susceptible to Marek’s disease
B21 haplotype
Chickens are genetically resistant to Marek’s disease
Marek’s disease - Clinical features - Neurolymphomatosis
Enlargement of nerve trunks. Vagus, brachial, and sciatic nerves. Usually unilateral. Edematous, grey or yellowish. Lameness, droopy wings, paresis legs, limberneck, torticollis (twisted neck) and incoordination
Marek’s disease - Clinical features - Visceral lymphomatosis
Diffuse or nodular lymphoid tumors may be seen in various organs, particularly the liver, spleen, gonads, heart, lungs, kidney, muscle, and proventriculus. Bursa is only rarely tumorous and more frequently is atrophic. The absence of bursal tumors helps distinguish this disease from lymphoid leukosis.
Marek’s disease - Clinical features - Ocular lymphomatosis
Graying of the iris (aka gray eye, cat eye, or pearl eye). Interference with normal pupillary constriction and dilation. Due to T-cell infiltration and partial or total blindness.
Marek’s disease - Diagnosis
Cell culture, CAM inoculation
Marek’s disease - Control (Vaccination)
REPORTABLE DISEASE!
Most widleyused vaccine consists of Turkey Herpesvirus (HVT). Bivalent vaccines consists of HVT and either SB-1 or 301B/1 strains of Gallid herpesvirus 3 (Serotype, avirulent strain). Most protective commercial vaccine is CVI988/Rispens.
Subfamily: Betaherpesvirinae
Porcine Herpesvirus-2
Subfamily: Betaherpesvirinae - Properties
- Slow replicating virus
- Associated wit chronic infections
- Infected cells are often enlarged (cytomegaly)
- Maintained in latent form in secretory glands and lymphoreticular cells
- Often associated with continuous viral excretion
Porcine Herpesvirus-2
Inclusion Body Rhinitis also known as Porcine cytomegalovirus (PCMV)
PCMV - Hosts
Pigs from ages 2 to 10 weeks old or piglets less than 3 weeks old
PCMV - Transmission
Inhalation and transplacental
PCMV - Pathogenesis
Primary site of replication is the nasal mucous glands and epithelial cells of upper respiratory tract. Endothelial cell damage and necrosis: petechial hemorrhages and edema.
Infected cells are enlarged and possess intranuclear inclusion bodies, especially in nasal glands. Hence, known as Inclusion Body Rhinitis.
PCMV - Clinical signs - piglets
Less than 3 weeks old. Mucopurulent rhinitis. Violent sneezing, respiratory distress, conjunctivitis, shivering, mouth breathing and variable death loss. Appear weak, anemic or stunted and there may be edema around the throat and tarsal joints.
Subfamily: Gammaherpesvirinae
Malignant Catarrhal Fever (MCF). Includes
- Alcephaline herpesvirus-1 (AHV-1)
- Ovine herpesvirus-2 (OvHV-2)
Subfamily: Gammaherpesvirinae - Properties
Lymphotrophic (replicate in B or T cells). Slowly cytopathic for epithelial and fibroblastic cells, causing death without production.
MCF- Synonyms
Bovine Malignant Catarrh, Malignant Head Catarrh
MCF - Host
Highly fatal disease of cattle and some wild ruminants (deer, bison, antelope)
MCF - Alcephaline herpesvirus-1
Wildebeest associated. Transmits to cattle. Occurs in most African countries. DOES NOT CAUSE DISEASE TO WILDEBEEST. Epizootic and seasonal (based on wildebeest calving season)
(def. epizootic - denoting a disease that is temporarily prevalent and widespread in an animal population.)
MCF - Ovine herpesvirus-2
OvHV-2 is transmitted from sheep to cattle. Occurs year round.
REMEMBER!
In Africa, MCF is predominantly found where cattle are in close contact with blue or black wildebeest, while outside Africa, it is usually associated with contact between sheep and susceptible species.
MCF - AHV-1 - Transmission
Wildebeest to cattle. Present in nasal and ocular secretion of young wildebeest in a cell free state. Ingestion of pasture contaminated with nasal or ocular secretions from young wildebeest. Direct or close contact, inhalation or aerosol with young wildebeest. Direct or close contact with wildebeest during calving (virus in cell-free state in young). Virus in cell-associated form in adult wildebeest, so rarely transmitted from adults.
MCF - OvHV-2 - Transmission
Not known. Presumably by inhalation or ingestion.
MCF - Cattle
Cattle are dead end hosts. Cattle have cell-associated virus, but not cell-free virus, in secretions. this may explain the noncontagious nature of MCF when contact occurs with MCF affected cattle.
MCF - Pathogenesis
Infection followed by cell-associated viremia. Lymphoid proliferation and infiltration. Necrotizing vasculitis. CD8+ T cells are predominant cells associated with vascular lesions.
MCF - Clinical signs - Peracute
Sudden death. “Head and eye” form may not appear. High fever, acute gastroenteritis.
MCF - Clinical signs - Head and eye form - Early stages
Reddened eyelids, bilateral corneal opacity, crusty muzzle, nares, nasal discharge, salivation.
MCF - Clinical signs - Head and eye form - Later stages
Erosions on the tongue and hard palate. Necrosis and erosion of the buccal papillae.
MCF - Other Clinical signs
Joints, superficial lymph nodes swell, horn, hoof, coverings slough, nervous signs, incoordination, head pressing, nystagmus, hyperesthesia (extreme sensitivity to touch), enlarged prescapular lymph node, sloughing of hoof coverings.
MCF- Alimentary/Intesinal form
Death occurs from severe diarrhea. Diarrhea is rarely observed in wildebeest derived MCF, but is more commonly in sheep associated MCF.
MCF - Mild form
inoculated animals, recovery expected
MCF - Necropsy findings
Zebra striping: bovine colon. Severe longitudinal linear congestion of the mucosa.
