HERPESVIRUSES

Zeinab Abd Elkhalek

Ass. Prof. of Medical Microbiology & Immunology

Faculty Of Medicine, Cairo University
 Family Herpesviridae
(Herpesviruses)
A large family of DNA viruses, which often cause
life-long latent recurring infections which progress
slowly.

Types of Herpesviruses
• Herpes simplex virus (HSV-1, HSV-2).
• Varicella-Zoster virus (VZV).
• Epstein-Barr virus (EBV).
• Cytomegalovirus (CMV).
• Human herpesvirus 6 (HHV6).
• Human herpesvirus 7 (HHV7).
• Human herpesvirus 8 (HHV8).
 HSV-1 & HSV-2
Similar in morphology & structure, but
can be distinguished by the following:
• Location of the lesion:
– HSV-1 above the waist
– HSV-2 below the waist.
Pathogenesis & Clinical Picture
Primary HSV Infections
)Exposure to the virus for the first time(

• Probably transmitted by direct contact.

• Involves the mucous membrane of the mouth,

lips, skin of face, nose, eyes and genital tract.

• Clinically, appears as vesicles on an

erythematous base, vesicles rupture and its
contents dry forming crusts which finally heal
(within 7-10 days) without scarring.
Pathogenesis & Clinical Picture
Latent Infections

• Replication occurs at the site of the entry of the virus in the

epithelium.

• Virus particles are transported along the axons to the sensory

(dorsal root) ganglion where some virus particles are able to
establish a latent infection.

• HSV-1 latency is in the trigeminal ganglion while in HSV-2

latency is in the sacral ganglia.

• Latency remains for the life-time of the host.

Pathogenesis & Clinical Picture
Reactivation & Recurrence
• Reactivation of the latent virus:
– may be restricted to asymptomatic shedding
– or may produce clinically obvious disease (at any site innervated by
the affected neurons).

• Provoked by various stimuli: fever, UV exposure, sunlight,

trauma, stress, immuno-suppression and in case of HSV-2
by sexual intercourse.

• The presence of specific antibody reduces the severity -but

not the recurrence- of infection (cell-to-cell spread).
Oral manifestation of herpes simplex infection
1. Primary herpes simplex infection “herpetic
stomatitis” (HSV-1 HSV-2)
a. Pain in the mouth & throat, lymphadenopathy and fever
b. Then vesicles appear on the oral mucosa, tongue and gingiva
c. vesicles rupture to form small round or irregular superficial
ulcers with erythematous haloes and grayish-yellow bases.
d. Mouth is very painful, eating & swallowing are difficult.
e. Lesions heal (within 7-10 days) without scarring.

2. Secondary herpes simplex infection “herpes

labialis” (HSV-1, HSV-2)
a. Provoked by various stimuli: fever, UV exposure, sunlight,
trauma, stress, immuno-suppression and in case of HSV-2 by
sexual intercourse.
Oral manifestation of herpes simplex infection
b. The lesion develops at the muco-cutaneous junction of the
lip or the skin adjacent to nostrils, preceded 24 hours, by
itching or burning sensation.
c. Blisters develop, enlarge, enlarge, coalesce, rupture,
encrusted and heal within 10-14 days

3. Herpetic dermatitis and herpetic whitlow (HSV-1 ,

HSV-2)
a. Localized lesion characterized by pain and purities
b. Multiple vesicles appear ,persist 4-5 days and burst,
resultant crusting heal within 2-3 weeks
c. Dentists who escaped exposure in childhood may contract
herpetic dermatitis in the form of herpetic whitlow on the
finger from patients who have herpes infection .
 Herpetic stomatitis
Genital herpes Herpes simplex I

Herpetic Whitlow
Herpes Labialis
Laboratory Diagnosis of HSV Infections
• Isolation of the virus on tissue culture.

• Direct detection of HSV in vesicle fluid by electron

microscopy.

• Detection of viral DNA by PCR.

• Detection of viral antigen by direct immunefluorescence or

ELISA.

• Serological diagnosis to detect IgM antibodies that indicates

recent infection or reactivation.
 Treatment
• Idoxuridine (IDU) topically is used in the treatment
of eye and skin infections.

• Acyclovir & vidarabine: inhibit viral DNA

synthesis. Acyclovir (Zuvirax) is available for topical,
oral and I.V. use.

• Foscarnet:
– inhibit HSV DNA polymerase.
– Used in treating acyclovir-resistant HSV infections.
 Prevention

• Immunocompromised (e.g., transplant

recipients) are given acyclovir to prevent viral
reactivation.

• Caesarean section: recommended for mothers

with active genital HSV infection to avoid
neonatal infection.
VARICELLA-ZOSTER VIRUS
(VZV)
 VARICELLA-ZOSTER VIRUS
(VZV)

Infection with VZV presents in two

clinical forms:
– The primary infection; varicella
(chickenpox) is a generalized eruption,
– The reactivation infection; zoster
(shingles) is a localized form.

N.B.: There is only one antigenic type of VZV.

Pathogenesis & Clinical Features 1
1. Varicella (chickenpox)
• The virus enters by droplet infection.
• The patient is usually a child 4-10 years old
• Incubation period: 2 weeks.
• the typical rash of varicella appears first on the trunk then
spread to the face and limbs.
• The skin rash is initially macular and rapidly evolves
through papules to clear vesicles.
• The vesicles changes to pustules which dry to form scabs
which heal without scar formation.
• The disease usually runs a benign course.
Varicella (Chickenpox)
Varicella (Chickenpox)
Pathogenesis & Clinical Features 3
2. Zoster (shingles)
• It results from reactivation of latent varicella infection in the
neurons.
• The virus reaches the ganglion from the periphery by
travelling along nerve axons or by blood during viraemic
stage of varicella infection during childhood.
• The disease usually occurs in older people

• It manifests as painful vesicular eruption, unilateral and

confined to one dermatome, usually thoracic or lumbar.
• The condition may follow trauma to the spinal cord or may
complicate lymphomas, leukaemia or immunosuppression.
Zoster (Shingles)
 Treatment
• Acyclovir (IV) is effective in the
treatment of varicella and zoster.

• It is not used for all cases, but

indicated in the following conditions:
– Immunocompromised patients.
– Ophthalmic zoster (to avoid corneal
scarring).
– Neonatal infection.
 Prevention & Control

• Acyclovir & interferon: are given to

immune deficient children.
• VZ immune globulin (VZIG): should be
given to contacts of cases to prevent
development of disease.
• Live attenuated varicella vaccine
(Varivax): given as one dose for
children 1-12 years of age.
 EPSTEIN-BARR VIRUS (EBV)
HHV- 4
• Widespread and mostly asymptomatic.

• The virus is excreted and transmitted via

the saliva and multiply in the
oropharyngeal mucosa.

• EBV receptors are also present on B-

lymphocytes.
 EBV Diseases
• Infectious mononucleosis (glandular
fever).

• Others:
– Nasopharyngeal carcinoma.
– Burkitt’s lymphoma.
– Oral hairy leukoplakia (in AIDS patients).
– Hodgkin’s disease.
– T-cell lymphoma.
 Infectious Mononucleosis
(Glandular Fever)
Pathogenesis & Clinical Features

• Incubation period: 30-50 days.

• Fever, sore throat, skin rash and cervical
lymphadenopathy which becomes generalized with
or without hepatosplenomegaly.
• The virus attacks B cells resulting in the appearance
of antibodies.
• This is followed by a marked T cell response which
is detected as large number of atypical lymphocytes
in the peripheral blood.
Oral manifestation of Epstein-Barr virus
(EBV) infections
• At the onset, the throat is painful and
congested.

• Clusters of fine petechial hemorrhage at the

junction of the hard and soft palates.

• A white pseudomembrane and oral ulceration

may develop.
 Laboratory Diagnosis
1. Blood picture: A high total leucocytic count (up to
25,000/cmm) with predominance of monocytes and
atypical lymphocytes.
2. Detection of heterophil antibodies: which
agglutinate sheep or horse RBCs (Paul Bunnell test or
monopost test).
3. Definitive diagnosis requires the demonstration of IgM
to EBV capsid antigen or rising titre of IgG to both
viral capsid antigen (VCA) or EB nuclear antigen (EBNA).
4. Detection of EBV nucleic acids in patient’s saliva or
throat washing using DNA probes or PCR.
 Prevention & Control

A subunit vaccine
based on major
viral glycoprotein
is under trial.
 CYTOMEGALOVIRUS (CMV)
HHV- 5
– The name “cytomegalovirus“ was chosen on account of
the swollen state of virus-infected cells.

– The virus is widespread.

– Primary infections occur in 40-60% of individuals and the

virus persists in the host for life (latent infection).

– Reactivation is common.

– Transmission; Transplacental (congenital), Close

contact, Sexual intercourse, Breast feeding, Blood
transfusion, Organ transplantation
Human Herpes Virus 6 (HHV6)
Human Herpes Virus 7 (HHV7)
• HHV6 is the cause of a common disease of infancy called
Exanthem subitum (roseola infantum or sixth disease).

• It is characterized by high fever and skin rash, sore throat

and cervical lymphadenopathy.
Roseola Infantum
 Human herpes virus 8
(Kaposi’s Sarcoma-Related
Herpesvirus)
This virus was identified in 1994 from tissue
of Kaposi’s sarcoma in patients with AIDS.
Kaposi’s Sarcoma