2/24/2019

Herpesviruses
Dr. ABDEL-RAHMAN YOUSSEF, MBBCh, MD, PhD
Assistant Professor in Microbiology & Immunology
Faculty of Dentistry
Umm Al-Qura University

Objectives
• Properties of Herpesviruses

• Herpes Simplex Viruses:

– Epidemiology, pathogenesis, clinical manifestation
– Laboratory diagnosis and management

• Varicell -Zoster Virus (VZV):

– Varicella and Zoster
– Laboratory diagnosis and management

• Human Herpes Virus 8 and Kaposi's sarcoma

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Types of human herpesviruses:

1. Herpes simplex virus 1 HSV-1
2. Herpes simplex virus 2 HSV-2
3. Varicella-zoster virus VZV
4. Epstein-Barr virus EBV
5. Cytomegalovirus CMV
6. Human herpesvirus 6 HHV-6
7. Human herpesvirus 7 HHV-7
8. Human herpesvirus 8 HHV-8

Properties of Herpesviruses
• Enveloped double stranded DNA viruses, icosahedral
protein capsid about 100nm
• Set up latent or persistent infection following primary
infection
• Reactivation are more likely to take place during periods
of immunosuppression
• Both primary infection and reactivation are likely to be
more serious in immunocmpromised patients

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Herpesvirus Particle

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

Epidemiology of Herpes Simplex Viruses (HSV)

• Man is the only natural host for HSV

• HSV are two types: HSV-1 and HSV-2
▪ HSV-1 spreads by contact with infected saliva
▪ HSV-2 spreads by sexual contact or to the newborn during
birth
▪ Generally HSV-1 causes infection above the belt and HSV-2
below the belt
▪ Primary infection occurs in children below 5 years for HSV-1
or at the age of sexual activity for HSV-2 and is usually
subclinical (asymptomatic) in most individuals

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Pathogenesis

▪ HSV multiplies locally in the mucus membrane or abraded

skin causing cytolysis, necrosis & multinucleated giant cell
▪ HSV infect neurons – travel via axon to nerve ganglia where
it establishes latency (persist for life)
▪ Latency: the HSV-1 establishes latency in trigeminal
ganglia whereas HSV-2 in sacral ganglia
▪ Reactivation - many triggers can provoke a recurrence
including physical or psychological stress, infection;
especially pneumococcal and meningococcal infection,
fever, irradiation, and menstruation

Clinical Manifestations

Clinical manifestations of HSV include:

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

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Oral-facial Herpes
Oral-facial Herpes include Acute Gingivostomatitis
and Herpes labialis (cold sore)
Acute Gingivostomatitis
–The commonest manifestation of
primary herpetic infection
– Usually seen before 6 years of age
–Most children are asymptomatic
–The condition is highly contagious
–Erythematous gingiva, bleeding of the
gum and pain
–Clusters of small erupted vesicles
throughout the mouth.
–Fever & cervical lymphadenopathy
–Usually a self-limiting disease which lasts
around 13 days

• Herpes labialis (cold sore)

– Herpes labialis (cold sore) is a
recurrence of oral HSV
– A prodromal of tingling,
warmth or itching followed by
redness, papules and then
vesicles

• Herpetic whitlow
– Pustular lesion on the fingers
of medical staff a acquired
from the patients

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Genital Herpes
• Genital lesions may be primary or recurrent
• Caused by HSV-1 or HSV-2
• Characterized by vesicles and ulcers on external genitalia

Recurrent genital herpes

infection on penis

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.

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Ocular Herpes
Ocular Herpes include:
• HSV conjunctivitis
• Primary and recurrent HSV keratitis →dendritic ulcers
• Iridocyclitis: inflammation of the iris and the ciliary body
• Chorioretinitis: inflammation of the choroid and retina
• Cataract

Dendritic ulcer
with fluorescein
staining

HSV conjunctivitis

Herpes Simplex Encephalitis (HSE)

• Herpes Simplex encephalitis is one of the most serious
complications of herpes simplex disease.
• <95% caused by HSV1
• Higher rate in immunocompromised
• Virus enter CNS by neurotropic spread from the periphery
• Affect children and young adult
• Diagnosis: by polymarse chain reaction (PCR) of CSF
• Treatment: IV acyclovir is given in all cases of suspected
HSE before laboratory results are available.

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Laboratory Diagnosis
• Direct Detection
– Electron microscopy of vesicle fluid - rapid result but
cannot distinguish between HSV and VZV
– Immunofluorescence of skin scrapings - can distinguish
between HSV and VZV
– PCR - now is used routinely for the diagnosis of herpes
simplex encephalitis

• Virus Isolation in cell culture

– HSV-1 and HSV-2 are among the easiest viruses to
cultivate.
– Cytopathic Effect of HSV in cell culture
– It usually takes only 1 - 5 days for a result to be available

Cytopathic Effect of HSV in cell culture: Positive immunofluorescence test for

Note the ballooning of cells. (Linda HSV antigen in epithelial cell. (Virology
Stannard, University of Cape Town, Laboratory, New-Yale Haven Hospital)
S.A.)

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Management
Antiviral chemotherapy is indicated for:
1. Severe primary infection
2. Disseminated infection
3. Sight is threatened
4. Herpes simplex encephalitis
Acyclovir
It is the drug of choice
It is available as I.V. , Oral, Ophthalmic ointment
Cream (HSV infection of the skin & mucous membranes)

Foscarnet : for acyclovir resistant cases

Varicella- Zoster Virus (VZV)

• Cause 2 diseases: Varicella and Zoster

• Varicella is the primary disease characterized by
generalized rash
• Zoster is the recurrent form and manifested by localized
rash
Varicella Zoster

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Pathogenesis
• The Varicella- Zoster Virus (VZV) gains entry via the
respiratory droplets where multiply in the respiratory
mucosa and spreads via blood to the skin where it
causes widespread vesicular rash
• Incubation period: 14 days
• Following the primary infection, the virus remains latent
in the cerebral or posterior root ganglia
• The virus reactivates in the ganglion and tracks down
the sensory nerve to the area of the skin innervated by
the nerve, producing a rash in the distribution of a
dermatome (Zoster or shingles)

Varicella (chickenpox)
• Primary infection results in varicella
• Presents with fever, lymphadenopathy and widespread
vesicular rash which evolve from papules, vesicles, pustules
and finally crusts
• The rash starts on trunk then spread to the limbs and face
• The rash is typical and diagnosis is made on clinical grounds

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Herpes Zoster (Shingles)

• Herpes Zoster mainly affect a single skin dermatome
• Usually occur after age of 50
• The latent virus reactivates in a sensory ganglion and
tracks down the sensory nerve
• Characterized by a localized unilateral painful skin rash
with vesicles in the dermatomal distribution
• It may last for months (post-herpetic neuralgia)
• Herpes zoster affecting the eye and face may pose great
problems

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Laboratory Diagnosis
The diagnosis is mainly clinical
Laboratory diagnosis is required only for atypical
presentations, specially in the immunocompromised patients
– Direct detection by
• Electron microscopy
• Immunofluorescense on skin scrapings
– Serology
• Presence of VZV IgG is indicative of past infection and
immunity
• Presence of IgM is indicative of recent primary infection

Management
• Uncomplicated varicella is a self limited disease and
requires no specific treatment.
• Treatment (Acyclovir, valacyclovir, foscarnet) should be
given promptly to:
– Immunocompromised individuals with varicella infection
– Normal individuals with serious complications such as
pneumonia and encephalitis.
– Ophthalmic zoster
– Neonate
– all patients over 50 years of age presenting with herpes
zoster

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Human herpesvirus 6 (HHV-6)

• HHV-6 has high affinity for CD4 lymphocytes.
• HHV-6 comprises 2 forms, A and B
• HHV-6 receptor is CD46
• HHV-6 B causes the childhood illness roseola infantum
• Roseola is characterized by 3-5 days of high fever that resolves
abruptly and followed by development of a rash
• A blanching macular or maculopapular rash develops, starting
on the neck and trunk and spreading to the face & extremities
• Roseola is diagnosed clinically
• Self-limited disease

Human Herpes Virus 8

• HHV-8 is associated with Kaposi's sarcoma (KS)

• Kaposi's sarcoma is a cancerous tumour of the connective
tissue and is often associated with AIDS
• The tumours most often appear as bluish-red or purple
bump on the skin and oral mucosa

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