Herpesviruses

Department of Microbiology and

Parasitology
• Herpes Simplex Virus (HSV) types 1 and 2
• Varicella-Zoster Virus (VZV)
• Cytomegalovirus (CMV)
• Epstein-Barr virus (EBV)
• Herpesvirus 6 and 7 (HHV 6, HHV 7)
• Herpesvirus 8 (Kaposi sarcoma-associated
herpesvirus)
 Structure and Composition
• Large viruses
• Indistinguishable by EM
• Core of dsDNA in the form of a toroid
surrounded by a protein coat with
icosahedral symmetry
• Nucleocapsid surrounded by envelope
• Tegument: amorphous, asymmetric
structure bet capsid and envelope
 Structure and Composition
• Striking feature: sequence arrangement
• Genome possess terminal and internal
repeated sequences
• Some members undergo genome
rearrangements givingrise to genome
“isomers”
 Properties of Herpesviruses
• Enveloped double stranded DNA viruses; linear
• Genome : long and short fragments orientated in
either direction, giving a total of 4 isomers
reiterated sequences

Virion: spherical, icosahedral

Protein: > 35 proteins in virion
Envelope: with viral glycoproteins, Fc receptors
Replication: nucleus
Outstanding charac: encode many enzymes
establish latent infections
persist indefinitely in hosts
frequent reactivation in immunocomporomised
some are cancer-causing
Properties of Herpesviruses
• Set up latent or persistent infection following
primary infection

• Reactivation - more likely during periods of

immunosuppression

• Both 1º infection and reactivation are likely to be

more serious in immunocompromised patients.
Properties of Herpesviruses
Three subfamilies:
– Alphaherpesviruses: HSV-1, HSV-2, VZV
rapid growth, latency in sensory ganglia

– Betaherpesviruses: CMV, HHV-6, HHV-7

slow growth ; restricted host range

– Gammaherpesviruses: EBV, HHV-8

growth in lymphoblastoid cells
 Classification of Human Herpesviruses
subfamily Latent genus Common name
infection

Alphaherpesvirinae neurons Simplexvirus Herpes Simples Virus 1, 2

(HSV 1, 2)
Varicellovirus Varicella Zoster Virus (VZV)

Betaherpesvirinae Glands, Cytomegalovirus Cytomegalovirus (CMV)

kidneys
Lymphoid Roseolovirus Human herpesvirus 6 and 7
tissue (HHV 6, 7)
Gammaherpesvirinae Lymphoid Lymphocryptovirus Epstein-barr virus (EBV)
tissue
Rhadinovirus Kaposi’s sarcoma-associated
herpesvirus (HHV 8)
 Herpesvirus Particle
HSV-2 virus particle.
ALL herpesviruses have
identical morphology and
cannot be distinguished
from each other under
electron microscopy.

(Linda Stannard, University of Cape Town, S.A.)

Herpes Simplex
Viruses
 Properties
• Belong to the -herpesvirus subfamily of
herpesviruses

• Double stranded DNA enveloped virus with a

genome of around 150 kb
 HSV
• 2 distinct types: HSV 1 and HSV 2
• React serologically but some unique
proteins exist for each type
• Different mode of transmission:
– Type 1: contact, saliva
– Type 2: sexual, maternal genital infection
to newborn
 Properties
• The genome of HSV-1 and HSV-2
- share 50 - 70% homology.
- share several cross-reactive epitopes
with each other.
- also antigenic cross-reaction with VZV.
• Man is the only natural host for HSV.
 Epidemiology (1)
• HSV - spread by contact
(shed in saliva, tears, genital and other secretions).

• Most common form of infection results from a

KISS given to a child or adult from a person
shedding the virus.

• Primary infection
- usually trivial or subclinical in most individuals.
- disease mainly of very young children ( < 5 yrs.)
 Epidemiology (1)
• Two peaks of incidence,
1. 0 - 5 years
2. late teens (sexual activity commences).

• 10% of the population acquires HSV infection

through the genital route and the risk is
concentrated in young adulthood.
 Epidemiology (2)
• Generally: HSV-1 causes infection above the
belt
HSV-2 below the belt

• Clinical isolates :
- 40% from genital sores are HSV-1
- 5% of strains isolated from the facial area
are HSV-2.
(data is complicated by oral sexual practices)
 Epidemiology (2)
• Following 1º infection,
45% of orally infected individuals and
60% of patients with genital herpes
will experience recurrences.

• actual frequency of recurrences varies widely

between individuals
mean number of episodes per year : 1.6
• HSV must encounter mucosal surfaces
or broken skin in order for an infection
to be initiated
 Pathogenesis
• Primary infection, HSV spreads locally and a
short-lived viraemia occurs, whereby the
virus is disseminated in the body.
– Spread to the craniospinal ganglia occurs.
• The virus then establishes latency in the
craniospinal ganglia.
– HSV 1 latent infection in trigeminal ganglia
– HSV 2: sacral ganglia
• The exact mechanism of latency is not known
 Pathogenesis
• Reactivation - triggers can provoke a recurrence.
These include
– physical or psychological stress,
– Infection: especially pneumococcal and meningococcal,
– fever,
– irradiation; including sunlight, and
– menstruation.
 Clinical Manifestations
HSV is involved in a variety of clinical
manifestations which includes
1. Acute gingivostomatitis
2. Herpes labialis (cold sore)
3. Ocular herpes
4. Herpes genitalis
5. Other forms of cutaneous herpes
7. Meningitis
8. Encephalitis
9. Neonatal herpes
 Acute Gingivostomatitis and Herpes
Labialis
• Acute Gingivostomatitis
– Most common manifestation of primary herpetic infection.
– Pain and bleeding of the gums.
• 1 - 8 mm ulcers with necrotic bases
• Neck glands enlarged, accompanied by fever.
– Usually a self limiting disease which lasts around 13 days.
• Herpes labialis (cold sore)
– Following primary infection, 45% of orally infected individuals will
experience reactivation.
– Herpes labialis (cold sore) is a recurrence of oral HSV.
– Prodrome of tingling, warmth or itching at the site usually heralds
the recurrence; 12 hours later, redness appears followed by
papules and then vesicles.
 HSV
Gingivostomatitis

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Herpes labialis

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 Ocular Herpes
HSV causes a broad spectrum of ocular
disease, ranging from mild superficial lesions
involving the external eye, to severe sight-
threatening diseases of the inner eye.
• Primary HSV keratitis – dendritic ulcers
• Recurrent HSV keratitis
• HSV conjunctivitis
• Iridocyclitis, chorioretinitis and cataract
 Genital Herpes
• Genital lesions may be primary, recurrent or initial.
• Sites: penis, vagina, cervix, anus, vulva, bladder, sacral
nerve routes, spinal nerves and meninges
– Genital lesions prone to 2º bacterial infection
– eg. S. aureus, Streptococcus, Trichomonas and C.albicans.
• Dysuria: common complaint
– Urinary retention: in severe cases
• Local sensory nerves may be involved; leads to radiculitis.
• A mild meningitis may be present.
• Recurrence of genital herpes: 60%
– Recurrent lesions in perianal area tend to be numerous and
persists longer than their oral HSV-1 counterparts.
Genital Herpes
 Herpes Simplex Encephalitis
 One of the most serious complications of HSV disease
 2 forms:
– Neonatal: global involvement; brain is almost liquefied.
• mortality rate approaches 100%.
– Focal disease: temporal lobe most commonly affected
• appears in children and adults; arise from reactivation of virus
• mortality rate is high (70%) without treatment.

• Utmost importance: make a diagnosis of HSE early.

– IV acyclovir : given in all cases of suspected HSE before
laboratory results are available.
 Neonatal Herpes Simplex (1)
• Incidence varies from country to country
– US: 1 in 4000 live births
– UK: 1 in 10000 live births in the UK
• Baby infected perinatally during passage through the birth
canal.
• Premature rupturing of the membranes: recognized risk factor.
• Risk of perinatal transmission: greatest when there is a florid
primary infection in the mother.
• Smaller risk from recurrent lesions in mother: lower viral load
and the presence of specific antibody
• Other sources: oral lesions from the mother or a herpetic
whitlow in a nurse.
75% of cases occurs as newborn comes in contact with
Herpetic lesions in the birth canal
 Neonatal Herpes Simplex (2)
• Spectrum: mild disease, localized to skin --> fatal
disseminated infection.
• Infection : particularly dangerous in premature infants.
• Organs involved in disseminated disease:
– Liver, adrenals and the brain.
– Brain involvement: prognosis is severe;
• encephalitis is global; brain may be liquefied.
• Survivors : residual disabilities.
• Give Acyclovir in all suspected cases of neonatal HSV
infection.
• Prevention: offer caesarean section to mothers with florid
genital HSV lesions.
Neonatal Herpes Simplex
 Other Manifestations
• Disseminated herpes simplex: more likely in
immunocompromised individuals
– vesicular lesions resembles that of chickenpox
– Involved organs other than skin: liver, spleen,
lungs, & CNS
 Other Manifestations
• Other cutaneous manifestations include
– Eczema herpeticum: potentially a serious disease
that occurs in patients with eczema
– Herpetic whitlow : arise from implantation of the
virus into the skin, typically affect fingers
– “Zosteriform herpes simplex”: rare presentation
where HSV lesions appear in a dermatomal
distribution similar to herpes zoster

Herpes gladiatorum: lesions on the bodies of wrestlers

 Other Manifestations
eczema herpeticum :

Herpetic whitlow
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 Laboratory Diagnosis
• Direct Detection
– EM of vesicle fluid: rapid result but cannot distinguish
between HSV and VZV
– IF of skin scrapings: distinguish between HSV and
VZV
– PCR: diagnosis of herpes simple encephalitis
• Virus Isolation
– HSV-1 and HSV-2 are among the easiest viruses to
cultivate; takes only 1 - 5 days
• Serology
– Not that useful in acute phase: takes 1-2 weeks
before antibodies appear after infection
– Used to document to recent infection
Cytopathic Effect of HSV in Positive immunofluorescence test
cell culture: Note the
for HSV antigen in epithelial cell.
ballooning of cells. (Linda
Stannard, University of Cape (Virology Laboratory, New-Yale
Haven Hospital)
Town, S.A.)
 Management
General indications for antiviral chemotherapy
• where primary infection is especially severe
• where there is dissemination
• where sight is threatened, and
• herpes simplex encephalitis
 Management
Acyclovir – drug of choice for most situations at present
• I.V. (HSV infection in normal and
immunocompromised patients)
• Oral (treatment and long term suppression of
mucocutaneous herpes and prophylaxis of HSV in
immunocompromised patients)
• Cream (HSV infection of the skin and mucous
membranes)
• Ophthalmic ointment
 Management
Famciclovir and valacyclovir – oral only, more
expensive than acyclovir.

Other older agents – e.g. idoxuridine,

trifluorothymidine, Vidarabine (ara-A).
• These agents are highly toxic and is suitable for
topical use for ophthalmic infection only
Varicella- Zoster Virus
 Properties
• Belong to the alphaherpesvirus subfamily of
herpesviruses
• Double stranded DNA enveloped virus
• Genome size 125 kbp, long and short
fragments with a total of 4 isometric forms.
• One antigenic serotype only, although there
is some cross reaction with HSV.
 Epidemiology
• Primary varicella (chickenpox) is an endemic disease;
classic disease of childhood
highest prevalence : 4 - 10 years old age group.
• Varicella is highly communicable, attack rate of 90%
in close contacts.
• Most people become infected before adulthood but
10% of young adults remain susceptible.
• Herpes zoster: occurs sporadically and evenly
throughout the year.
 Pathogenesis
• Entry via respiratory tract; spreads to lymphoid
system.
• After IP of 14 days, virus arrives at its main target
organ, the skin
• Following primary infection, virus remains latent in
cerebral or posterior root ganglia.
– 10 - 20%: single recurrent infection after several decades.
• Virus reactivates in ganglion and tracks down the
sensory nerve to skin area innervated by the nerve,
producing a varicella form rash in the distribution of
a dermatome.
 Varicella Zoster Virus
• Primary infection results in varicella (chickenpox)
• Incubation period of 14-21 days
• Manifestations:
– fever, lymphadenopathy. a widespread vesicular rash.
• Clinical features are characteristic
– diagnosis made on clinical grounds alone.
• Complications rare
– occurs more frequently and with greater severity in adults and
immunocompromised patients.
– Most common complication : secondary bacterial infection
– Severe complications: life threatening - viral pneumonia,
encephalitis, and hemorrhagic chickenpox.
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Rash of Chickenpox
 Herpes Zoster (Shingles)
• Herpes Zoster mainly affect a single dermatome
• May occur at any age; majority are > 50 years of age.
• Latent virus reactivates in sensory ganglion and tracks
down sensory nerve to the appropriate segment.
• Eruption of vesicles in dermatome accompanied by
intense pain and may last for months (postherpetic neuralgia)
• Eye and face involvement: pose great problems
• HZ among immunocompromised: problematic
– reactivation occurs earlier in life; multiple attacks; complications
• Complications: rare, include encephalitis and
disseminated herpes zoster.
Shingles
 Congenital VZV Infection
• 90% of pregnant women already immune, therefore
primary infection is rare during pregnancy
• Primary infection during pregnancy carries a greater
risk of severe disease, in particular pneumonia.
First 20 weeks of Pregnancy
• 3% chance of transmission to the fetus
• recognized congenital varicella syndrome:
– Scarring of skin
– Hypoplasia of limbs
– CNS and eye defects
– Death in infancy normal
Congenital VZV Infection
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 Neonatal Varicella
• VZV can cross placenta in late stages of pregnancy to
infect the fetus congenitally.
• Neonatal varicella: vary from mild disease to a fatal
disseminated infection.
• If rash in mother occurs > 1 week before delivery,
sufficient immunity transferred to the fetus.
• VZIg should be given to susceptible pregnant women
who had contact with suspected cases of varicella.
• VZIg should also be given to infants whose mothers
develop varicella during the last 7 days of pregnancy or
the first 14 days after delivery.
 Laboratory Diagnosis
Clinical presentation: characteristic
Laboratory diagnosis: required only for atypical
presentations, particularly in the immunocompromised.
– Virus Isolation: rarely carried out; results available after 2-3 wks
– Direct detection - electron microscopy may be used for vesicle
fluids but cannot distinguish between HSV and VZV.
– IF on skin scrapings can distinguish between the two.
– Serology – (+) VZV IgG : past infection and immunity.
(+) IgM : recent primary infection.
 Management
• Uncomplicated varicella: self limited ; no specific
treatment.
– Acyclovir : accelerate resolution of the disease
– Indications: immunocompromised;
• Those with serious complications: pneumonia and encephalitis.
• Herpes zoster in healthy individual: not a cause for
concern.
– management of postherpetic neuralgia can be problematic
– International Herpes Management Forum recommends
antiviral therapy be offered routinely to all over age 50 years
presenting with herpes zoster.
– 3 drugs for herpes zoster: acyclovir, valacyclovir, and
famciclovir. There appears to be little difference in efficacy
between them.
 Prevention
• Preventive measures: considered at risk of
contracting severe varicella infection e.g. leukemic
children, neonates, and pregnant women
• Where urgent protection is needed, passive
immunization should be given.
– Varicella Zoster immunoglobulin (VZIG) is the preparation of
choice but it is very expensive.
– A live attenuated vaccine is available.
• safe, even in children with lekaemia provided that they are in
remission.
Cytomegalovirus
 Properties
• Belong to the betaherpesvirus subfamily of
herpesviruses
• Double stranded DNA enveloped virus
• Nucleocapsid 105nm in diameter, 162 capsomers
• Genomic structure of CMV is similar to other
herpesviruses, consisting of long and short
segments which may be orientated in either
direction, giving a total of 4 isomers.
• A large no. of proteins are encoded for, the precise
number is unknown.
 Epidemiology
• CMV: one of the most successful human
pathogens
– transmitted vertically or horizontally usually with little
effect on the host
• Transmission: in utero, perinatally or postnatally
• Once infected, person carries the virus for life
which may be activated from time to time, during
which infectious virions appear in urine and
saliva.
• Reactivation can also lead to vertical
transmission.
 Epidemiology
• also possible for people who have experienced
primary infection to be reinfected with another or
the same strain of CMV; this reinfection does not
differ clinically from reactivation
• In developed countries with a high standard of
hygiene, 40% of adolescents are infected and
ultimately 70% of the population is infected.
• In developing countries, over 90% of people are
ultimately infected.
 Pathogenesis
• Once infected, virus remains for life w/c may be
reactivated from time to time
• Perinatal infection: acquired mainly through infected
genital secretions, or breast milk.
– 2 - 10% of infants infected by age 6 months
– Perinatal infection: 10x more common than congenital infection.
• Postnatal infection mainly occurs through saliva.
• Sexual transmission may occur
• Transmission also through blood and blood products, and
transplanted organ
 Clinical Manifestations
• Congenital infection: result in cytomegalic inclusion
disease
• Perinatal infection - usually asymptomatic
• Postnatal infection - usually asymptomatic
– Minority of cases: a syndrome of infectious mononucleosis may
develop: fever, lymphadenopathy, and splenomegaly
– heterophil antibody test (-) ; atypical lymphocytes may be found
in the blood.
• Immunocompromised patients: transplant recipients and
AIDS patients prone to severe CMV disease such as
pneumonitis, retinitis, colitis, and encephalopathy.
• Reactivation or reinfection usually asymptomatic
EXCEPT in immunocompromised patients.
 Congenital Infection
• Definition of congenital CMV infection: isolation of CMV from the
saliva or urine w/in 3 wks of birth
• CMV is
– most common congenital viral infection; affects 0.3 - 1% of all live
births
– 2nd most common cause of mental handicap after Down's
syndrome; responsible for more cases of congenital damage than
rubella.
• Transmission to fetus may occur following primary or recurrent
CMV infection;
– 40% chance of transmission to fetus following primary
infection.
• May be transmitted to fetus during all stages of pregnancy.
• No evidence of teratogenicity, damage to the fetus results from
destruction of target cells once they are formed.
 Cytomegalic Inclusion Disease
• CNS abnormalities:
– microcephaly, mental retardation, spasticity, epilepsy,
periventricular calcification

• Eye: chorioretinitis and optic atrophy

• Ear: sensorineural deafness
• Liver: hepatosplenomegaly & jaundice due to hepatitis.
• Lung: pneumonitis
• Heart: myocarditis
• Thrombocytopenic purpura, Hemolytic anaemia
• Late sequelae in individuals asymptomatic at birth:
hearing defects and reduced intelligence.
 Laboratory Diagnosis (1)
• Direct detection
– biopsy specimens: histologic examination for CMV
inclusion antibodies or for presence of CMV antigens;
• sensitivity may be low.
– pp65 CMV antigenemia test: routinely used for rapid
diagnosis of CMV infection in immunocompromised
– PCR for CMV-DNA: used in some centers but there
may be problems with interpretation.
 Laboratory Diagnosis (2)
• Virus Isolation
– conventional cell culture: gold standard
• requires up to 4 weeks for result.
– More useful: rapid culture methods such as the DEAFF
test - provide a result in 24-48 hours.
• Serology
– (+) CMV IgG antibody : past infection.
– IgM : primary infection
also be found in immunocompromised
patients with reactivation
Specimens for Laboratory
Diagnosis
 Treatment
• Congenital infections:
– “Ganciclovir used to treat some congenitally infected infants
but is not recommended routinely” (Red Book 27th ed.)
• Potential toxicity of long term use
• Perinatal and postnatal infection: not necessary to
treat such patients
• Immunocompromised patients: early diagnosis of CMV
infection and give prompt antiviral therapy
– Anti-CMV agents in current use are ganciclovir, foscarnet,
and cidofovir.
 Prevention
• No licensed vaccine available.
– Candidate live attenuated vaccine known as the Towne strain
• concern: administering a live vaccine which can become latent and
reactivates.
• Prevention in transplant recipients: complicated and varies from
center to center. It may include the following measures.
– Screening and matching the CMV status of the donor and
recipient
– Use of CMV negative blood for transfusions
– Administration of CMV immunoglobulin to seronegative
recipients prior to transplant
– Give antiviral agents such as acyclovir and ganciclovir
prophylactically.
Epstein Barr Virus
(EBV)
Epstein-Barr Virus (EBV)
• Belong to the gammaherpesvirus subfamily
• Nucleocapsid:100 nm in diameter, 162 capsomers
• Membrane is derived by budding of immature
particles through cell membrane and is required for
infectivity.
• Genome: linear double stranded DNA;172 kbp
• Viral genome does not normally integrate into the
cellular DNA but forms circular epitomes which reside
in the nucleus.
• The genome is large enough to code for 100 - 200
proteins but only a few have been identified.
 Epidemiology
• Two epidemiological patterns seen with EBV.
• Developed countries : 2 peaks of infection
preschool children aged 1 - 6
adolescents and young adults aged 14 - 20
Eventually 80-90% of adults are infected.
 Developing countries: much earlier age so that by the
age of two, 90% of children are seropositive.
• Transmitted by contact with saliva (kissing)
 Pathogenesis
• Lifelong carrier state develops once infected, whereby a low grade
infection is kept in check by the immune defenses.
• Low grade virus replication and shedding: demonstrated in epithelial
cells of the pharynx of all seropositive individuals.
• EBV: able to immortalize B-lymphocytes in vitro and in vivo
• Few EBV-immortalized B-cells can be demonstrated in the
circulation which are continually cleared by immune surveillance
mechanisms.
• EBV is associated with several very different diseases where it may
act directly or one of several co-factors.
 Disease Association
1. Infectious Mononucleosis
2. Burkitt's lymphoma
3. Nasopharyngeal carcinoma
4. Lymphoproliferative disease and lymphoma in the
immunosuppressed.
5. X-linked lymphoproliferative syndrome
6. Chronic infectious mononucleosis
7. Oral leukoplakia in AIDS patients
8. Chronic interstitial pneumonitis in AIDS patients.
 Infectious Mononucleosis
• Primary EBV infection:
– usually subclinical in childhood
– adolescents & adults: 50% chance this syndrome (of IM) will develop.
• IM: self-limited disease: fever, lymphadenopathy & splenomegaly;
– In some: jaundice (due to hepatitis); (+) atypical lymphocytes in the blood
• Complications: rare but may be serious
– e.g. splenic rupture, meningoencephalitis, pharyngeal obstruction.
• Chronic IM may occur where eventually patient dies of
lymphoproliferative disease or lymphoma.
• Diagnosis of IM: heterophil antibody test and/or detection of EBV IgM.
• NO specific treatment.
 Burkitt’s Lymphoma (1)
• Burkitt's lymphoma (BL): occurs endemically in parts of
Africa (most common childhood tumor) & Papua New
Guinea.
– usually seen: children aged 3-14 yrs
– responds favorably to chemotherapy.
• Restricted to areas with holoendemic malaria. Therefore
it appears that malaria infection is a cofactor.
• Multiple copies of EBV genome and some EBV antigens
can be found in BL cells and patients with BL have high
titres of antibodies against various EBV antigens.
• BL cells show a reciprocal translocation between long arm of
chromosome 8 and chromosomes 14, 2 or 22.
 Nasopharyngeal
Carcinoma
• Nasopharyngeal carcinoma (NPC):
– malignant tumor of squamous epithelium
of nasopharynx;
– prevalent in S. China: most common tumor in men & 2nd common in
women.
• Rare in most parts of the world, though pockets occur in N. and C.
Africa, Malaysia, Alaska, and Iceland.
• Multiple copies of EBV genome and EBV EBNA-1 antigen can be
found in cells of undifferentiated NPC.
– Patients with NPC have high titres of antibodies against various EBV Ag
• Environmental and genetic cofactors in NPC.
• NPC usually presents late and thus the prognosis is poor.
• In theory NPC can be prevented by vaccination.
 Immunocompromised Patients
• After primary infection, EBV maintains steady low
grade latent infection in the body: virus
reactivates when a person becomes
immunocompromised
• In some: lymphoproliferative lesions and
lymphoma may develop; lesions tend to be
extranodal, in unusual sites: GIT & CNS
• Transplant recipients - EBV is associated with
development of lymphoproliferative disease and
lymphoma.
 Immunocompromised Patients
• AIDS patients - EBV is associated with oral leukoplakia
and with various Non-Hodgkin’s lymphoma.
• Ducan X-linked lymphoproliferative syndrome - occurs
exclusively in males who had inherited a defective gene in
the X-chromosome .
– This condition accounts for half of the fatal cases of IM.
 Diagnosis
• Acute EBV infection : heterophil antibody test and/or
detection of anti-EBV VCA IgM.
• Burkitt’s lymphoma: histology.
– tumor can be stained with antibodies to lambda light chains which
reveal a monoclonal tumour of B-cell origin. In over 90% of
cases, the cells express IgM at the cell surface.
• NPC: histology.
• determination of titre of anti-EBV VCA IgA in screening for
early lesions of NPC and also for monitoring treatment.
– patients with non-specific ENT symptoms who have elevated
titres of EBV IgA should be given a thorough examination
 Vaccination
• A vaccine against EBV which prevents primary EBV infection
should be able to control both BL and NPC.
• Must be given early in life.; also be useful in seronegative organ
transplant recipients and those developing severe IM, such as the
male offspring of X-linked proliferative syndrome carriers.
• The antigen chosen for vaccine development is the MA antigen gp
340/220 as antibodies against this antigen are virus neutralizing.
• This vaccine is being tried in Africa.
Other Human Herpes
Viruses
Properties of HHV-6 and 7
• Belong to the -herpesvirus subfamily of
herpesviruses
• Double stranded DNA genome of 170 kbp
• Main target cell :
T-lymphocyte, although B-lymphocytes may
also be infected.
Properties of HHV-6 and 7
• HHV-6 and HHV-7 share limited nucleotide
homology and antigenic cross-reactivity.

• It is thought that HHV-6 and HHV-7 are

related to each other in a similar manner to
HSV-1 and HSV-2.
Epidemiology and Pathogenesis
• HHV-6 and HHV-7 : ubiquitous, found worldwide.
• Transmitted mainly through contact with saliva
and through breast feeding.
• HHV-6 and HHV-7 infection are acquired rapidly
after the age of 4 months when the effect of
maternal antibody wears off.
Epidemiology and Pathogenesis
• Adulthood, 90-99% of the population had been
infected by both viruses.

• HHV-6 and HHV-7 remains latent in the body

after primary infection and reactivates from time
to time.
 Clinical Manifestations
(1)
• 1º HHV-6 infection :
associated with Roseola infantum
• Infants : 4 months and 2 yrs.
• A spiking fever develops over a period of 2 days
followed by a mild rash. The fever is high
enough
to cause febrile convulsions.
• May be complicated by encephalitis.
Clinical Manifestations (2)
• If 1º infection is delayed until adulthood, there
is a small chance that an IM-like disease may
develop in a similar manner to EBV and CMV.
• NO firm evidence linking HHV-6 to lymphomas or
lymphoproliferative diseases.
Clinical Manifestations (2)
• NO firm disease association with HHV-7 at
present.
• Although both viruses may be reactivated in
immunocompromised patients, it is yet uncertain
whether they cause significant disease since
CMV is almost invariably present.
 Roseala Infantum

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Roseola is a childhood illness caused by two strains of herpes virus.

Common signs of roseola are fever and a rash on the trunk and neck.
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Human Herpesvirus 6 (Including Roseola) and 7. Roseola

rash in a 10-month-old infant. Seizures are not uncommon
during the febrile phase of primary infection
 Diagnosis and Management
• Roseola infantum : clinical
• very few virology laboratories offer a diagnostic
service for HHV-6 or HHV-7 infection.
• virus isolation : complicated

• serology : mainstay of diagnosis ;

specific IgM and IgG are detected.

• NO specific antiviral treatment

 Human Herpes Virus 8
• Belong to the gammaherpesviruses subfamily of
herpesviruses
• Originally isolated from cells of Kaposi’s sarcoma
(KS)
• associated with KS as well as some lesser known
malignancies such as Castleman’s disease and
primary effusion lymphomas
 Human Herpes Virus 8
• HHV-8 DNA is found in almost 100% of cases of
Kaposi’s sarcoma
• Most patients with KS have antibodies against
HHV-8
• seroprevalence of HHV-8 : low among general
population but is high in groups of individuals
susceptible to KS, such as homosexual
• does not have a ubiquitous distribution.
Kaposi’s Sarcoma