Herpesviridae

This is a large, diverse family of DNA viruses that infect humans and a wide variety of animal
hosts. They are large in size and are noted for their ability to cause latent infections. They are
divergent with regard to genome sequence and proteins, biological properties, but are similar in
overall virion structure and genome organization.
Viral Characteristics
 They are enveloped, double stranded DNA viruses (100 - 200nm in diameter) with an
icosahedral capsid.
 The virions consist of four structural units: 1) the core of DNA around that is wrapped a
protein fibrilar spool; 2) a capsid composed of 12 pentameric and 150 hexameric
capsomeres; 3) an amorphous protein layer between the capsid and the envelope; and 4) the
envelope.
 The envelope has projections (spikes) evenly distributed over its surface (see Fig. 1).
 The dsDNA is used as a template for the production of progeny genomes and mRNAs,
 Following fusion of the viral envelope with the cell membrane, the nucleocapsid migrates to
the cell nucleus, where replication takes place.
 Viral transcription is divided into immediate early, early, and late transcription. The
structural proteins and the genome (DNA or RNA) are assembled into icosahedral or helical
virions, then released.
 Certain host cells can prevent the transcription of genes and thus the viral genome persists,
does not replicate, and th e host cell doesn’t die. This constitutes a form of viral latency.
 All herpesviruses thus far examined have the capacity for latency in host cells.
 There is no common antigen for all members.

Figure 1. Herpesviridae (100 - 200 nm). Between the capsid and the envelope there is a protein-
filled region known as the tegument.
Herpesvirus Infections: General
All herpesviruses are thought to be capable of establishing latent infections. The classic example is
human herpesvirus 1 (HSV-1) which infects of the dorsal root ganglia. The virus is latent between
episodes of "cold sores". During latency only a small region of the viral genome is expressed,
athough no protein has been unequivocally identified as a product of this transcription. The
mechanism of reactivation of infection is not understood.
Some virus species infecting eukaryotic hosts are cell-associated and a small number are
oncogenic. Many infections are silent or mild in natural hosts but serious in other hosts. For
example, pseudorabies virus is a broad host range herpesvirus that causes fatal encephalitis in a
wide variety of animal species but not in its natural host, the adult pig.
Herpesviruses are widespread and are frequently recovered in the diagnostic laboratory as they can
be readily cultivated in cell cultures; some produce pocks on the chorioallantoic membrane. Only
those herpesviruses causing significant animal diseases are discussed below.
A general rule is that every animal species harbors at least one herpesvirus.
Classification
The family Herpesviridae is divided into three subfamilies, Alphaherpesvirinae, Betaherpesvirinae,
and Gammaherpesvirinae.
Alphaherpesvirinae have a relatively short replication cycle (< 24 h), a variable host range, and
usually cause rapid destruction of cultured cells. Viruses belonging to this subfamily establish
latent infections in neural cells. Most herpesviruses of veterinary importance are found in the genus
Varicellovirus.
Betaherpesvirinae contains the genera Cytomegalovirus, Muromegalovirus, and Roseolovirus of
little veterinary significance. Unlike the Alphaherpesvirinae, this group of viruses has a relatively
slow replication cycle (>24 h), a narrow host range, and causes a slow destruction of cultured cells.
Infected cells are often greatly enlarged and may contain cytoplasmic as well as nuclear inclusions.
These viruses establish latent infections in lymphoreticular and secretory gland cells.
Gammaherpesvirinae contains the genera Lymphocryptovirus (marine and fresh water fish) and
Rhadinovirus (disease in marmosets and monkeys).
 Alphaherpesvirinae (Subfamily)
Simplexvirus:
o Bovine herpesvirus 2:
 Bovine ulcerative mammillitis, pseudolumpy-skin disease
o Cercopithecine herpes 1 (B virus of monkeys):
 Infects Asian macaque monkeys naturally; has caused rare fatal encephalitis
in monkey handlers.
 Varicellovirus:
o Bovine herpesvirus 1:
 Infectious bovine rhinotracheitis, pustular vulvovaginitis / balanoposthitis
o Bovine herpesvirus 5:
 Causes meningo-encephalitis in cattle, particularly in South America
o Porcine herpesvirus 1:
 Pseudorabies or Aujesky’s disease
o Canine herpesvirus 1:
 Canine herpesvirus infection
o Equine herpesvirus 1:
 Equine herpesvirus abortion
o Equine herpesvirus 3:
 Equine coital exanthema
o Equine herpesvirus 4:
 Equine rhinopeumonitis
o Feline herpesvirus 1:
 Feline viral rhinotracheitis
 Marek’s disease-like viruses:
o Gallid herpesvirus 2:
 Marek’s disease
 Infectious laryngo-tracheitis-like viruses:
o Gallid herpesvirus 1:
 Infectious laryngotracheitis
 Betaherpesvirinae (Subfamily)
 o No viruses of significance in domestic and farm animals.
 Gammaherpesvirinae (Subfamily)
Rhadinovirus
o Alcelaphine herpesvirus 1:
 Malignant catarrhal fever in cattle, deer and other ruminants in Africa;
natural host is the wildebeest.
 Ovine herpesvirus 2
o Malignant catarrhal fever in cattle and some wild ruminants; sheep are natural host;
occurs worldwide.
 Unassigned Genera
o Porcine herpesvirus 2:
 Inclusion body rhinitis
o Anatid herpesvirus 1:
 Duck viral enteritis

Simplexvirus
Bovine Ulcerative Mammillitis
(Bovine herpes mammillitis, pseudolumpy skin disease, Allerton virus)
Cause
Bovine herpesvirus 2.
Occurrence
It occurs sporadically, mainly in dairy cattle, worldwide.
Transmission
By milkers, contaminated milking machines and mechanically by biting insects.
Pathogenesis
After inoculation into the skin or subcutaneous tissue the virus replicates locally without systemic
spread.
Clinical & Pathologic Features
Bovine ulcerative mammillitis primarily affects dairy cattle causing a marked loss of milk
production. It is characterized by edema of teats followed by vesicle formation and subsequent
erosion of the teat and udder epithelium. Vesicles usually rupture within 24 hours and yield a
serous exudate. Secondary bacterial infection may occur if no special care is taken. Scabs begin to
form at four days, and healing occurs under the scab with recovery usually in 3 - 4 weeks. Milking
may prevent scab formation and consequently delay healing.
Face and muzzle lesions may occur in nursing calves.
The Allerton strain of BHV-2 was originally isolated in Africa from cattle with generalized skin
infections. This form of the disease, referred to as pseudolumpy-skin disease, occurs in tropical and
subtropical regions.
Diagnosis
 Clinical specimens: Vesicular fluid, scabs, and scrapings of lesion.
 A rapid diagnosis of herpes mammillitis can be achieved by the electron microscopic
demonstration of herpesvirus in distilled water lysates of lesion material.
  The virus can be isolated in cell cultures of bovine origin, but grows best at reduced
temperature. Identification is accomplished by serum neutralization and fluorescent
antibody tests. The virus produces large, characteristic syncytia in cultured cells.

Prevention
 Vaccines are not available.
 Control is best accomplished by sound milking practices. First-lactation cows should be
milked first. Antiseptic teat-dipping and routine disinfection of the milking machine should
be practiced. Any affected animal should be kept in isolation.

Varicellovirus
Infectious Bovine Rhinotracheitis (IBR)
(Infectious pustular vulvovaginitis / balanoposthitis)
Cause
Bovine herpesvirus 1.
Two subtypes of IBRV (BHV-1) virus have been defined based on monoclonal antibody
binding/restriction enzyme analysis. They are designated:
BHV-1.1 (respiratory subtype)
BHV-1.2 (genital subtype).
Although BHV-1.1 is referred to as the respiratory subtype, it is also associated with abortion and
very rarely with encephalitis. After the identification of BHV-5 as a major cause of
meningoencephalitis in cattle, a question has been raised whether some events of encephalitis in the
past attributed to BHV-1 were indeed caused by this virus or by BHV-5, since most diagnostic
reagents are not capable of distinguishing between these viruses.
Subtype BHV-1.2 is further divided into BHV-1.2a and BHV-1.2b. The former-may cause abortion
whereas the latter seems not to. Both have been associated with vulvovaginitis and balanoposthitis.
Occurrence
Infection by BHV-1 occurs in cattle worldwide, with the exception of some European countries that
have eradicated the infection. Bovine herpesvirus 5 infection is discussed separately.
Transmission
Infection occurs via the respiratory and genital routes. Spread is by direct and indirect contact
(fomites) and aerosol droplets. The infection may be spread from infected bulls by coitus and
artificial insemination. Frozen semen is an optimal condition for virus survival.
Pathogenesis
Replication takes place in the mucous membrane of the upper respiratory tract/genital mucosa and
virus is shed in nasal/genital secretions. Semen may be contaminated during the ejaculation. Local
nerve cell endings are infected and the virus is transported to trigeminal/sacral ganglia where it
establishes a lifelong latent infection. Viremia is rarely detected, but it does occur, as infection of
pregnant cows may lead to fetal infection and abortion. Once infected, the animals become lifelong
carriers of the virus. The latent infection may be reactivated periodically, with or without clinical
signs; the virus is transported back to the site of entry and is shed with potential transmission to
other animals.
Clinical & Pathologic Features
IBR is an acute, contagious, widespread disease that is manifested in the following forms:
rhinotracheitis, pustular vulvovaginitis / balanoposthitis and conjunctivitis. Neurological disease is
attributed to another related virus, previously classified as a subtype of BHV-1, and now classified
as BHV-5.
The respiratory form of the disease is most common. It has a sudden onset with high temperature.
There is congestion and severe inflammation of the mucous membranes with serous ocular and
nasal discharges. The morbidity is high in unvaccinated (nonimmune) herds but mortality is
generally low. Recovery is usually uneventful in well-managed herds within about 14 days. Under
stressful conditions (e.g., feedlots), secondary bacterial infection may lead to a severe tracheitis
with diphtheritic membrane and bronchopneumonia.
The genital form, pustular vulvovaginitis and balanoposthitis, is characterized by inflammation of
the genital mucosa and development of small pustules that coalesce and ulcerate. Infections may be
mild or subclinical.
Abortion or stillbirths, which are infrequent, may occur 1 - 3 months postinfection.
The conjunctivitis form is common with occasional involvement of the cornea, and a
panophthalmitis.
Bovine herpesvirus 5, initially identified Australia, is now considered the cause of fatal encephalitis
in calves, a disease frequent in some South American countries.
Diagnosis
 Clinical specimens: Nasal and ocular swabs; vaginal and preputial swabs; trachea and lung;
fetal liver, kidney, and lung; acute and convalescent sera. Specimens should be submitted
for virus isolation in cell culture.
 A presumptive diagnosis is often made on the basis of clinical signs and lesions.
 A definitive diagnosis requires demonstration of viral infected cells by
immunofluorescence, isolation, and identification of the virus, or the demonstration of a
significant increase in IBR antibody levels between acute and convalescent serum samples.
 Immunofluorescence is the preferred method for the diagnosis of IBR abortions because the
virus is often nonviable owing to advanced autolysis of fetal tissues.
 The virus is easily isolated from clinical specimens by the inoculation of cell cultures of
bovine origin. The virus induces a well-recognized CPE in tissue culture.
 BHV-1 and BHV-5 cannot be differentiated serologically by routine tests, since they
display an extensive serological cross-reactivity.

Prevention
 Modified live and killed vaccines often are available in combination with other bacterial
and viral antigens. The modified live vaccines are of two types, one that is administered
intramuscularly (IM) and one that is given intranasally (IN). The IN vaccine is
recommended for pregnant cows since it is safe for the fetus.
 In eradication programs deletion mutant vaccines (marker vaccines) have been used to
distinguish between vaccinal and natural antibodies using ELISA procedures.

Bovine Herpesvirus 5 Infection

Cause
Bovine herpesvirus 5.
Apparently latent infections are reactivated by various stresses including those associated with
transportation, weaning, and other management practices. In Brazil it is thought that some cases
result from reactivation of latent BHV 5 infection by polioencephalomalacia.
Occurrence
The disease occurs rarely in Australia and some European countries. In South America, particularly
in Brazil and Argentina, a number of outbreaks occur annually. Most outbreaks are in cattle seven
months to three years of age; occurrence in younger cattle is infrequent. Although single cases in
cattle up to six years of age have been reported they are uncommon. Up to 30% of animals in a
herd may be affected. The disease occurs independently of classic IBR.
Transmission
This is probably similar to that described above for IBR viruses.
The most probable ingress of infection is thought to be via the nose and olfactory nerve. Thus most
lesions involve the frontal cortex.
Clinical Features
The course is usually 4 - 7 days but may be as long as15 days. Clinical signs are mainly those of a
meningoencephalitis. Blindness, head pressing and deep depression are particularly characteristic.
The disease is almost always fatal.
Diagnosis
 Clinical specimens: Whole brain or portions from cerebrum, cerebellum and brain stem.
 The virus can be isolated from the brain and distinguished from IBR isolates as described
under the diagnosis of IBR above.
 Diagnosis may be made on the basis of clinical features and characteristic histopathologic
lesions in the brain. There is malacia of the cerebral cortex and encephalitis and meningitis
involves mainly the cerebrum and to a lesser extent the brain stem and cerebellum.
Inclusion bodies in astrocytes and neurons are frequently present.

Prevention
Although IBR vaccines containing bovine herpesvirus 1 are effective their use is not considered
cost-effective in view of the usual infrequency of the disease.
Pseudorabies (PR)
(Aujeszky’s disease)
Cause
Porcine herpesvirus 1 (also known as pseudorabies virus, PRV).
Occurrence
Hosts include swine, cattle, cats, dogs, horses, sheep, rats, mink, rodents, raccoons, skunks,
opossum and other animals. Rabbits are particularly susceptible to experimental inoculation. Dogs
and cats are also very susceptible to the infection and their death is often the first indication of the
presence of the virus in some swine herds. Swine (domestic and wild) are the natural host and only
known reservoir host.
The disease occurs worldwide and is widespread but often regional in distribution. Some European
countries have eradicated the infection recently, while others are in the process of eradication.
Canada is free of the disease as are most states of the USA.
Transmission
Direct contact between infected and susceptible swine appears to be the most important means of
spread. Aerosol droplets and fomites also spread the virus. Infected animals may shed virus for up
to a month in various secretions, milk and urine.
Infection in species other than swine is via skin or mucous membranes and by ingestion.
Pathogenesis
The virus multiplies in the mucous membrane of the nasopharynx and in the tonsils. Spread is to
the regional lymph nodes and to the CNS via axons of the cranial nerves. In virtually all infected
animals that survive acute infection the virus establish latent infection in tonsils and trigeminal
ganglia. In the acute disease a viremia follows introduction of the virus with rapid dissemination
throughout the body.
Transplacental infection of the fetus is common. As for BHV-1, the latent infection is the major
means for virus survival and transmission in nature, as it may be periodically reactivated.
Clinical & Pathologic Features
The severity of the disease in swine is inversely related to the animal's age. The morbidity in pigs
up to one month of age is very high and the mortality may be nearly 100%.
Young pigs usually have high temperature and nervous signs such as incoordination of hind limbs,
paddling movements and convulsions.
Older pigs, up to six months of age, are less susceptible and the mortality is usually less than 10%.
They may show respiratory and nervous signs.
Adult hogs may have an inapparent infection or may develop anorexia and mild signs of respiratory
infection.
Pregnant gilts and sows may experience reproductive failure, including abortions and stillbirths.
In cattle, sheep, dogs, cats and other subhuman mammals, the disease is highly fatal but not
contagious. These animals are called dead-end hosts. There is an intense itching at the site of
infection if infection is via the skin, followed by mania, encephalitis, paralysis, coma, and death.
Diagnosis
 Clinical specimens: brain, lungs, tonsil, spleen, kidney, liver, and serum. In animals other
than pigs, a portion of the subcutaneous tissue is taken from the site of pruritis and spinal
cord.
 Gross necropsy lesions consisting of small focal areas of necrosis are sometimes noted in
the liver and spleen of aborted fetuses and baby pigs infected with PR. Microscopic
examination of these tissues reveals the presence of intranuclear inclusions typical of
herpesvirus. A nonsuppurative meningoencephalitis is the most common microscopic
finding in pigs experiencing CNS signs.
 Fluorescent antibody tests on frozen sections of tissue are used for rapid diagnosis.
 Inoculation of infectious material subcutaneously into the rabbit produces an intense
pruritus at the site followed by death, usually in 3 - 6 days. This inhumane procedure is no
longer required.
 The virus can be propagated readily on the chorioallantoic membrane of chicken embryos,
and in pig kidney and other cell cultures producing cytopathic changes as early as 16 hours
postinoculation. The virus maybe identified by virus neutralization and fluorescent antibody
tests.
 Serum neutralization, latex agglutination, and ELISA tests are used for the detection of
antibody.

Prevention
 Modified live and inactivated vaccines are used as well as an intranasal vaccine used in
sows and neonates. Vaccination of the complete herd may be advisable.
 Efforts should be made to keep herds free of PR by purchasing replacement stock only from
certified free herds.
 Show animals and new additions should be isolated and serologically tested before
introduction to the herd.
  Genetically engineered (gene-deletion) vaccines are used in areas where the disease is
endemic. Deletion of the thymidine kinase gene renders the virus less able to replicate in
neurons. The advantage of gene-deleted vaccines over other modified live or killed PR
vaccines is that a special ELISA test can be used to differentiate vaccine induced antibody
from antibody resulting from natural infection.
 Eradication can be achieved by repeating a test with removal of positive animals until all
tests are negative.

Equine Rhinopneumonitis
(Equine herpesvirus 4 infection)
Cause
Equine herpesvirus 4 (EHV 4).
Occurrence
Equine rhinopneumonitis occurs frequently in horses throughout the world.
Transmission
Infection occurs by the respiratory route and spread occurs by direct or indirect contact, aerosol
droplets, and fomites.
Clinical & Pathologic Features
EHV 4 causes a usually mild respiratory disease principally observed in young horses up to two
years of age.
The incubation period is 2 - 10 days. Affected horses are febrile and display mild depression, nasal
discharge and rhinitis. In the absence of secondary bacterial infections, recovery is usually
uneventful in 1 to 3 weeks.
On rare occasions, infection of pregnant mares may result in abortion.
Latent infection of trigeminal ganglia occurs with EHV-4. The epidemiological consequences of
latent infection are the same as described for BHV-1 and PRV.
Diagnosis
 Clinical specimens: nasal swabs, whole blood, and acute and convalescent sera.
 Diagnosis of EHV 4 infection is confirmed by isolation of the virus in cell cultures of
equine origin. The demonstration of a significant increase in specific antibody between
acute and convalescent sera may also be used for diagnosis. EHV 4 is antigenically related
to EHV 1 and conventional serologic tests do not differentiate between these two agents.
Monoclonal antibodies are available to type isolates of the virus.
 A presumptive method to differentiate EHV 4 from EHV 1 is the inoculation of cell cultures
of equine (equine dermal cell line) and rabbit (RK-13 cell line) origin. The virus of EHV 1
grows in both cell types, but EHV 4 only grows in equine cells. An ELISA procedure has
been described to distinguish EHV 4 from EHV 1.

Prevention
 Modified live and killed virus vaccines are available for prophylaxis. Some vaccines
contain both EHV-4 ands well as EHV-1. These vaccines are usually given at 3 - 4 months
of age, with subsequent boosters at frequent intervals, especially while horses are young and
most susceptible.
 Risk of infection can be minimized by sound management practices.
 Newly purchased horses and horses returning from shows and racetracks should be
quarantined for several weeks.
Equine Herpesvirus Abortion
(Equine herpesvirus 1 infection, equine viral abortion)
Cause
Equine herpesvirus 1 (EHV-1).
Occurrence
Equine herpesvirus abortion (EHA) occurs frequently in horses worldwide.
Transmission
Spread is by direct and indirect contact and droplet infection.
Pathogenesis
Local infection may lead to a viremia with infection of the placenta, fetus and infrequently the
CNS. Many horses are latently infected with EHV-1 and EHV-4. Reactivation may occur after
various stresses and corticosteroid administration. Acute infection is followed by latent infection in
regional nerve ganglia.
Clinical & Pathologic Features
Although EHV 1 may cause mild respiratory tract infections in horses, most herpesviral-associated
respiratory disease is caused by EHV 4.
The virus of EHV 1 is principally associated with abortion and occasionally with neurologic
disease. Most EHV 1 abortions occur after seven months of gestation and about 2 - 4 weeks
following exposure of the pregnant mare.
Aborted fetuses often contain characteristic gross necropsy lesions of edematous lungs and small
tan areas of focal necrosis most readily observed in the liver, lungs, and spleen. The virus has a
predilection for vascular epithelium resulting in vasculitis and thrombosis.
Some infected foals are born live but usually exhibit loss of muscle tone, weakness, and the
inability to stand. Affected foals generally die within a matter of days.
Central nervous system dysfunction is a relatively rare complication of EHV 1 infection. Affected
horses may display clinical signs characterized by mild to severe ataxia. Recovery is usually
uneventful, but some affected horses may remain permanently impaired.
Diagnosis
 Clinical specimens: Fetal liver, lung, spleen, and thymus. Nasal swabs, whole blood,
cerebrospinal fluid, acute and convalescent sera, brain, and spinal cord from horses with
central nervous system disease.
 A presumptive diagnosis of EHV 1 abortion is often made on the basis of gross lesions
observed at necropsy. The finding of intranuclear inclusions in fetal tissues by
histopathologic examination is supportive.
 Confirmation is most easily and rapidly obtained by the demonstration of viral antigens in
infected cells by immunofluorescence examination of cryostat sections of affected tissue.
 The virus can be propagated in a variety of cell cultures, including those derived from the
horse and rabbit (RK-13 cell line). The ability to propagate EHV 1 in cell cultures of
nonequine origin provides a means to differentiate EHV 1 from EHV 4; the latter only
grows in equine cells. An ELISA procedure has also been described for the differentiation
of the two viruses.
 Diagnosis of EHV 1 associated central nervous system disease is more difficult. The virus
may be isolated from nasal swabs and blood from acutely affected horses, but the virus is
difficult to isolate from central nervous system tissue. Infection may be assumed if a
significant increase in specific antibody can be demonstrated between acute and
 convalescent sera. The histopathologic finding of vasculitis in central nervous system tissue
is suggestive.

Prevention
 Modified live and killed virus vaccines are available, but only the inactivated product is
labeled as a prophylaxis for abortion. It is usually given at 5, 7 and 9 months of pregnancy.
Other horses on the premises should also be vaccinated.
 Pregnant mares should be separated from other horses, and any mares that abort or develop
respiratory disease should be isolated. The use of foot-baths and clean coveralls by
attendants is advised.

Equine Coital Exanthema

(Equine herpesvirus 3 infection)
Cause
Equine herpesvirus 3.
Occurrence
Equine coital exanthema (ECE) has been reported in horse breeding populations worldwide.
Transmission
The virus is spread by coitus and possibly by flies feeding on infectious vaginal discharge.
Clinical & Pathologic Features
The disease is generally benign and clinically similar to infectious pustular vulvovaginitis /
balanoposthitis (IPVB) of cattle.
Secondary bacterial infections are common, but without complications the disease runs its course in
less than two weeks. Animals recovering from ECE may be become lifelong carriers.
Pustular vesicles and ulcers like those of IPVB are seen on the mucosa of the vulva, vagina, penis
and prepuce.
Many infections are subclinical or mild and may not be detected. There may be no fever or loss of
appetite.Ulcers heal in about 2 - 3 weeks and may leave characteristic white spots of unpigmented
skin that persist for life.
The virus can persist in clinically recovered horses in a latent state for long periods - probably for
the lifetime - and flare-ups may occur with consequent shedding and transmission.
Diagnosis
 Clinical specimens: Scraping from the affected mucosa of the vulva and penis. Acute and
convalescent sera.
 The disease is usually diagnosed clinically. Confirmation is by electron microscopy of
clinical material, isolation of the virus or the demonstration of a significant increase in
specific antibody between acute and convalescent sera (virus neutralization test).
 The virus can be propagated in cell cultures of equine origin.

Prevention
 Vaccines are not available.
 Affected horses are should be isolated.
 Ulcers will heal without treatment. Mild antiseptic lotions and ointments may be useful to
prevent secondary infection. Mating should be discontinued until ulcers are completely
healed.
Canine Herpesvirus Infection
Cause
Canine herpesvirus 1.
Occurrence
The disease is common, occurring in wild Canidae as well as domestic dogs.
Transmission
Infection of puppies takes place by contact with infectious oral, nasal or vaginal secretions during
or shortly after parturition. Infections are also thought to be acquired in utero.
Pathogenesis
The virus replicates in the nasal mucosa, tonsils and pharynx. Following viremia in neonates with
subnormal temperature there is multiplication of the virus in visceral organs. Latency occurs mainly
in trigeminal ganglia.
Clinical & Pathologic Features
Canine herpesvirus 1 produces a brief but severe illness of puppies characterized by a viremia with
an 80% mortality in puppies under one week of age. The severity of the illness in these young
puppies is related to their inability to adequately regulate body temperature or to mount a febrile
response to infection. Once these functions develop (2 - 3 weeks of age), puppies become resistant
to generalized infections because the virus does not grow well above 36°C.
The principal lesions noted in fatal infections are disseminated necrosis and hemorrhage involving
the kidney, liver, and lungs. Intranuclear inclusion bodies are observed in the alveolar and
interstitial cells of the lung and in cells adjacent to the areas of necrosis in the liver and kidney.
The virus has also been associated with mild vesicular vaginitis and tracheobronchitis. In utero
infections may result in abortion, stillbirths and infertility.
Diagnosis
 Clinical specimens: Lung, kidney.
 Petechial hemorrhages on the surface of the kidneys and pulmonary edema are
characteristic.
 The finding of typical inclusion bodies is diagnostically significant.
 A rapid diagnosis can be achieved by the fluorescent antibody staining of cryostat sections
of affected tissues.
 The virus can be easily propagated in cell cultures of canine origin (primary or MDCK
cells) and produces noticeable CPE.

Prevention
 Vaccination is not practiced.
 Prevention is best accomplished by reducing stress and minimizing contact between
pregnant bitches and other dogs.
 Newborn puppies should be maintained in a warm environment.

Feline Viral Rhinotracheitis

(Feline rhinotracheitis, feline coryza, feline influenza)
Cause
Feline herpesvirus 1.
Occurrence
Feline viral rhinotracheitis (FVR) is a frequently occurring, endemic, worldwide, contagious
disease of cats.
This virus causes about one-half of all respiratory disease in cats, and after acute infection cats
become latent carriers. In these animals, various stresses may trigger the excretion of the virus.
Transmission
The virus is transmitted by direct or indirect contact and the mode of infection is considered to be
inhalation.
Pathogenesis
Replication takes place initially in the oropharynx and conjunctivae followed by infection of the
mucous membrane of upper respiratory tract. Ordinarily there is no viremia.
Clinical & Pathologic Features
Feline rhinotracheitis virus affects cats most often between 3 - 18 months of age.
The incubation period is usually 2 - 5 days. Clinical signs include fever, anorexia, depression,
violent sneezing, conjunctivitis, lacrimation and nasal discharge. Frontal sinusitis and empyema
may occur as sequelae.
The virus may cause a serious generalized infection in young kittens similar to that seen in young
pups infected with canine herpesvirus 1.
Abortion (usually the sixth week of gestation), ulcerative keratitis, and bronchopneumonia often
occur.
Common lesions are focal necrosis with occasional ulceration involving nasal passages and
turbinates.
Intranuclear inclusions are seen in epithelial cells of nasal septum, tonsil, epiglottis, tradlea, and
nictitating membrane.
Cats that recover from the infection should be considered potential carriers.
A milder FVR may be seen in vaccinated animals.
Diagnosis
 Clinical specimens: Conjunctival scrapings and swabs, nasal swabs, lung and trachea from
necropsied cats.
 Most frequently diagnosed by clinical signs. Can be easily confused with feline calicivirus
infection.
 The finding of intranuclear inclusions in epithelial cells of affected mucous membranes is
diagnostically significant.
 A rapid definitive diagnosis can be obtained by the demonstration of viral infected cells in
conjunctival scrapings or in frozen sections of tissue by immunofluorescence.
 The virus can be cultivated in cell cultures of feline origin, in which it produces cytopathic
changes including intranuclear inclusions.
 Demonstration of a rising antibody titer in paired serum samples with serum neutralization
can be used for diagnosis.

Treatment
 Symptomatic and supportive.
 Antibiotics may be indicated for secondary bacterial infection.

Prevention
  Conventional attenuated and killed virus vaccines are available as well as intranasal
vaccines. Immunity is of short duration and several doses of vaccine are advised for young
animals.
 Killed virus vaccines are used for pregnant queens.

Marek’s Disease-like Viruses

Marek’s Disease (MD)
(Neural lymphomatosis, fowl paralysis)
Cause
Gallid herpesvirus 2. There are three serotypes of the virus; types 1 and 2 occur in chickens and
type 3 occurs in turkeys. Type 1 virus is oncogenic; types 2 and 3 are not.
Occurrence
Marek’s disease is common, worldwide, highly contagious disease affecting domestic fowl, turkeys
and quail. It occurs most often in chickens 8 - 20 weeks of age.
Transmission
Susceptible birds are infected via the respiratory tract through contact with viral contaminated
airborne dust particles. Virus replication and release occurs in the epithelial cells of feather follicles
and copious amounts of infectious virus are shed in dust and dander.
Pathogenesis
Initial infection of the respiratory tract occurs via inhalation of infectious dust. Three to five days
postinfection B lymphocytes of the bursa of Fabricius, spleen and thymus become infected. The
virus subsequently infects T lymphocytes of mostly the CD4 + phenotype; infection becomes latent
and the virus spreads throughout the host by a cell-associated viremia.
There is a secondary cytolytic infection of the feather follicle epithelium from which cell-free virus
is produced and shed in feather dander and debris.
Latently infected T lymphocytes are transformed leading to lesions of lymphomatosis in visceral
organs. The main target cells for transformation are CD4+ T cells and probably CD8+ T cells.
Genomic regions with the potential for transformation have been identified.
Clinical & Pathologic Features
The most common clinical sign associated with "classical" Marek's disease is motor paralysis
resulting from the effect of virus replication on peripheral nerves. Depending on the nerves
affected, there may be signs of progressive paralysis in the neck, wings, or legs.
Characteristic necropsy lesions noted with "classical" Marek's disease are enlarged peripheral and
autonomic nerves that appear yellow and translucent. Visceral tumors may or may not be present.
In the acute form of the disease, visceral tumors are common, often involving multiple organs, and
birds may die without obvious signs of paralysis. The most common organs affected are gonads,
kidney, liver, lung, muscle, and skin. Gross nerve lesions may not be noted.
Microscopically an infiltration of mononuclear cells is seen in affected tissues. Occasionally the
eye may be affected, resulting in blindness. This form of the disease is referred to as gray-eye or
ocular lymphomatosis.
Diagnosis
 Clinical specimens: Whole birds in extremis.
 Diagnosis is usually based on clinical signs and necropsy examinations. Marek's disease is
suspected if signs of paralysis or paresis are noted and if peripheral nerves are enlarged.
 If only visceral tumors are noted, the disease must be differentiated from lymphoid leukosis
by microscopic examination of tissues. With Marek's disease, there is usually perivascular
cuffing in the white matter of the cerebellum and an infiltration of mononuculear cells in
peripheral nerves. These lesions are absent in lymphoid leukosis.
Also the cytologic appearance of the lymphoid cells is different. In Marek's disease, there is
a mixture of mature and immature pleomorphic cells, whereas with lymphoid leukosis the
cells are uniformly "blast" cells.
Differential features of Marek's disease and lymphoid leukosis are summarized in Fig. 2.
 Viral and serologic procedures are usually not performed because the virus is present in
most chicken flocks.
 The three virus types can be propagated in chicken embryo kidney cells and in duck embryo
fibroblasts.

Figure -5. Differential features of Marek’s Disease (MD) and Lymphoid Leukosis (LL).
Prevention
 Marek’s disease is effectively prevented by vaccination of day-old chicks using serotype 3
Marek’s disease virus (turkey herpesvirus). Chicks should be reared in a clean environment
for 10 - 14 days until immunity is well established.
 In ovo vaccination is widely practiced; it is safe and effective. Embryonated eggs are
inoculated with an automatic device at 18 days of incubation.
 All three serotypes are used individually and in combination, bivalent and polyvalent, in
commercial vaccines. Recombinant vaccines have shown promise experimentally.
 Vaccine failures have been attributed to the emergence of unusually more virulent viruses.

Infectious laryngo-tracheitis-like viruses

Infectious Laryngotracheitis
Cause
Gallid herpesvirus 1.
Occurrence
Infectious laryngotracheitis (ILT) is a common, worldwide disease of chickens and pheasants.
Transmission
By direct and indirect contact and by droplet infection.
Pathogenesis
After initial infection, the virus replicates in the epithelium of the upper respiratory tact. The virus
travels along sensory nerves to become latent in trigeminal ganglia.
Clinical & Pathologic Features
The virus causes a mild to severe respiratory disease in young and older birds, usually in the fall
and winter months in Europe and North America.
Infection involves principally the larynx and trachea, resulting in coughing, gasping, and dyspnea.
Infected birds may cough up blood-stained mucus.
Morbidity is high but mortality does not usually exceed 15%.
There is marked congestion and hyperemia of the larynx and trachea. In the advanced disease
considerable caseous exudate present in the larynx and trachea; caseous cores and diphtheritic
membranes may also be present.
Intranuclear inclusion bodies are seen in the epithelial cells of the trachea. The tracheal lesions are
similar to those seen in the diphtheric form of fowlpox.
Infection with less virulent strains of ILT virus may only result in mild sinusitis and conjunctivitis.
Diagnosis
 Clinical specimens: Trachea and lung.
 A strongly presumptive diagnosis is made on the basis of clinical signs in severe outbreaks.
 The finding of typical herpesvirus intranuclear inclusions and characteristic gross lesions
are diagnostically significant.
 Electron microscopic examination of distilled water lysates of tracheal scrapings, and
fluorescent antibody examination are used for rapid diagnosis.
 The virus grows readily on the chorioallantoic membrane of embryonated chicken eggs.
The membrane becomes thickened and white plaques are noted.

Prevention
 Prevention is best accomplished by maintaining closed flocks.
 Modified live vaccines administered in drinking water or by aerosol sprays are widely used
to control the disease in layer flocks in areas where the virus is endemic. However,
vaccination doesn’t prevent the establishment and reactivation of latent infections.
 Birds that recover from the disease may remain latently infected.

Rhadinovirus
Malignant Catarrhal Fever (MCF)
(Snotsiekte - Africa)
Cause
Alcelaphine herpesvirus 1 causes malignant catarrhal fever (MCF) in Africa. Ovine herpesvirus 2
causes MCF in cattle in regions other than Africa.
Occurrence
Malignant catarrhal fever is a wide spread, infrequent, usually sporadic, often fatal disease.
It is caused by:
 Alcephine herpesvirus 1 causes the disease in Africa. Latent infections are present in the
wildebeest and other wild ruminants; it spreads from these to cattle.
 Ovine herpesvirus 2 causes the disease in sheep (natural host; subclinical infection) and
goats worldwide; the disease is transmitted from sheep to cattle.
The non-African form (Europe, North and South America and other regions) of MCF may
be transmitted to cattle and deer from sheep that shed virus during lambing. This form is
sometimes referred to as sheep associated MCF.
The incidence is not high. Except for feedlots, there are usually only one or two cases in a
herd at one time.

Transmission
As mentioned above the non-African MCF is considered to be transmitted to cattle and deer from
sheep that shed virus during lambing. Infection probably takes place via the respiratory route.
Pathogenesis
This is little understood. There is a cell-associated viremia and a dearth of virus in lesions. The
latter are thought to have an immunological basis. Although latency probably occurs there is no
evidence of recrudescence of infection.
Clinical & Pathologic Features
Most affected cattle may have the following signs: fever, depression, diarrhea, anorexia, rhinitis
with nasal discharge that becomes mucopurulent and encrusted. The skin of the muzzle becomes
eroded, and there is stomatitis, pharyngitis, laryngitis, and parotitis with salivation. After a short
febrile period; most cattle with the severe disease die within 10 days.
In addition to the lesions referred to the above, there may be edema of the meninges, perivascular
cuffing in other areas of the brain, enteritis, general lymphoid hyperplasia, and corneal opacity.
Gray foci may be seen in the kidneys and liver. The anterior cervical and retropharyngeal lymph
nodes may be hemorrhagic and edematous. Vasculitis is widespread.
Diagnosis
 Clinical specimens: Fresh leukocytes (buffy coat), fresh thyroid and adrenal tissue, serum.
 Diagnosis is usually based on clinical signs and pathologic changes. The usual sporadic
nature of the disease helps distinguish MCF from bovine virus diarrhea and rinderpest. The
history of sheep associated with cattle supports a diagnosis.
 Laboratory confirmation of MCF is difficult. Serologic tests, virus isolation, and molecular
techniques (polymerase chain reaction) are used, but these procedures are not available in
most diagnostic laboratories.
 The virus of the wildebeest-associated MCF has been isolated but is not ovine herpesvirus
2.

Prevention
 Vaccines are not available. The infrequency of the disease does not warrant use of a
vaccine.
 Cattle should be kept separate from sheep.
 A PCR assay has been used to detect infection in sheep.

Unassigned Genus
Inclusion Body Rhinitis
The cause is suid herpesvirus 2, which occurs widely in swine but clinical disease is infrequent.
The virus is shed in nasal secretions and transmission is by direct and indirect contact and by
aerosol droplets.
The disease is most severe in pigs up to two weeks of age.
Clinical signs include copious nasal discharge, sneezing, rhinitis and conjunctivitis with usual full
recovery.
Inclusion body rhinitis may be present with the more serious disease atrophic rhinitis.
Diagnosis
 Clinical specimens: Nasal swabs or scrapings and lung tissue.
 The disease is usually diagnosed histologically by demonstrating large basophilic
intranuclear inclusions in sections of or scrapings from the nasal mucosa. The inclusion
bodies can also be demonstrated in exfoliated epithelial cells obtained with nasal swabs.
 Electron microscopy is useful for demonstrating the virus in negative stained distilled water
lysates of nasal mucosa.
 The virus can be propagated in primary cell cultures of pig lung producing cytopathic
changes, including large intranuclear inclusions within 11 - 18 days postinoculation.

Prevention
 Vaccines are not available.
 The disease is infrequent in well managed herds.

Duck Viral Enteritis

(Duck plague)
Cause
Anatid herpesvirus 1.
Occurrence
Outbreaks in commercial geese and ducks can usually be traced to wild waterfowl. The disease,
which has been responsible for great losses, has been reported from North America, Europe and
Asia.
Transmission
This is by direct and indirect contact. Water contaminated with feces is the main source of
infection.
Clinical & Pathologic Features
Signs of this acute infection includes oculonasal discharge, photophobia, depression, inappetence,
thirst, and watery, blood-stained diarrhea. The mortality rate may be as high as 90%.
Recovered birds may shed virus for years.
Diagnosis
 Clinical specimens: Whole ducks in extremis or liver and mesenteric lymph nodes.
 A presumptive diagnosis is made on the basis of clinical signs and high death losses.
Lesions noted at necropsy are supportive. Characteristic hemorrhages are seen in many
organs, including the heart, liver, and intestine. Small white areas of focal necrosis may also
be noted in the liver. The finding of intranuclear inclusions is highly suggestive.
  The fluorescent antibody test on frozen sections of affected tissues is used for rapid
diagnosis.
 The virus can be propagated on the chorioallantoic membrane of duck embryonated eggs,
which die approximately four days after inoculation. One-day-old ducklings are susceptible
to experimental infection.

Prevention
 Modified live and killed virus vaccine are effective in prevention.
 Strict avoidance of contact with wild waterfowl.