1. HERPESVIRUSES
present by
Abdullah Naif
Ahmad Alzbali

2. • Herpes viruses are a leading cause of human viral
diseases, second only to influenza and cold viruses
• Are capable of causing overt disease or remaining silent for many
years only to be reactivated
• Name Herpes comes from the Latin herpes which, in turn, comes
from the Greek word herpein which means to creep
Introduction

3. Morphology
ü 100 – 200 nm in diameter, contains an icosahedral capsid
containing linear double stranded DNA genome
ü Surrounded by a lipid envelope containing peplomers
ü Between capsid and envelope is tegument

4. Classification of Human Herpesviruses
Subfamily Scientific name Common name
Alphaherpesvirinae Humanherpesvirus 1 Herpes simplex virus type 1
Humanherpesvirus 2 Herpes simplex virus type 2
Humanherpesvirus 3 Varicella-zoster virus
Betaherpesvirinae Human
Human
Human
Human
herpesvirus
herpesvirus
herpesvirus
herpesvirus
5
6
6a
7
Cytomegalovirus
-
-
-
Gammaherpesvirinae Humanherpesvirus 4 Epstein-Barr (EB) virus
Humanherpesvirus 8 Kaposi’s sarcoma associated
virus

5. Herpes Simplex Virus (HSV)
ü These are very large viruses and their genome (150 kb) encodes
at least 80 proteins
ü Almost any human cell type can be affected by HSV
ü The genome of HSV-1 and HSV-2 share 50 - 70% homology
ü Man is the only natural host
ü HSV-1 is usually associated with oral and occular lesions
ü HSV-2 is responsible for the majority of genital infections

6. Pathogenesis
Source of infection
Saliva, skin lesions or respiratory secretions from
patients or carriers
Mode of transmission
Direct contact with virus containing secretions or
with lesions
HSV 1: Kissing or saliva contaminated fingers HSV
2 : Sexual intercourse, congenital infection

7. ü HSV is shed in saliva, tears, genital and other secretions
ü The primary infection occurs through the skin, oral mucous
membranes, or eyes resulting in a vesicle formation
ü The virus spreads to draining lymphnodes producing
lymphadenitis
ü After primary infection the virus travels by retrograde intra-axonal
flow to sensory root ganglia
ü They settle within the neurons in the ganglia (trigeminal-HSV-1;
sacral-HSV-2)
ü The Herpesvirus DNA gets integrated into the host cell genome
ü These get reactivated when provoked by various stimuli
(common cold, fever, pneumonia, stress, exposure to sunlight
etc)

8. 1. Acute gingivostomatitis
2. Herpes labialis
3. Keratoconjunctivitis
4. Eczema herpeticum
5. Encephalitis
6. Dendritic keratitis
Diseases caused by HSV-1
Gingivostomatitis
Herpes labialis
(cold sore)

9. Diseases caused by HSV-2
1. Genital herpes (penis, urethra, cervix, vulva, vagina)
2. Neonatal herpes
3. Aseptic meningitis

10. Laboratory diagnosis
Specimens
1. Direct examination
2. Cell culture
3. Serology
4. PCR
Chemotherapy
v HSV infection can be treated with acyclovir (acycloguanosine)
v Valaciclovir and famciclovir are more effective oral agents
v When resistance to these drugs develop, drugs like trisodium
-phosphonoformate (Foscarnet) may be useful

11. Varicella-Zoster
ü Varicella (chickenpox) and herpes zoster (shingles) are caused
by a single virus
ü Chickenpox follows primary infection in a non-immune individual,
whereas herpes zoster is a reactivation of the latent virus
ü VZV is similar to the HSV in its morphology
ü Only one antigenic type of VZV is known

12. Pathogenesis
Source of infection
Patient with varicella or zoster Mode of
transmission Inhalation of respiratory droplets
Sometimes through conjunctiva
Varicella

13. • The virus is thought to gain entry via the respiratory tract and
spreads shortly after to the lymphoid system
• After an incubation period of 14 days, the virus arrives at its main
target organ, the skin
• Following the primary infection, the virus remains latent in the
cerebral or posterior root ganglia. In 10 - 20% of individuals, a
single recurrent infection occurs after several decades
• The virus reactivates in the ganglion and tracks down the sensory
nerve to the area of the skin innervated by the nerve, producing a
varicellaform rash in the distribution of a dermatome
Pathogenesis

14. • Primary infection results in varicella (chickenpox)
• Incubation period of 7-23 days
• Presents fever, a widespread vesicular rash mostly on the trunk
• The features are so characteristic that a diagnosis can usually be
made on clinical grounds alone
• Complications are rare but occurs more frequently and with
greater
severity in adults and immunocompromised patients
• Most common complication is secondary bacterial infection of the
vesicles
• Severe complications which may be life threatening include viral
pneumonia, encephalititis, and haemorrhagic chickenpox

15. Herpes Zoster (Shingles)
Ø Herpes Zoster mainly affect a single dermatome of the skin
Ø It may occur at any age but the vast majority of patients are more
than 50 years of age
Ø The latent virus reactivates in a sensory ganglion and tracks
down the sensory nerve to the appropriate segment
Ø The reactivation is associated with the inflammation of the nerve
which leads to neuritic pain that often precedes the skin lesions
Ø There is a characteristic eruption of vesicles in the dermatome
which is often accompanied by intensive pain which may last for
months (postherpetic neuralgia)

16. Ø Herpes zoster affecting the eye (ophthalmic zoster) and face
(Ramsay Hunt syndrome affecting the facial nerve) may pose
great problems
Ø As with varicella, herpes zoster in a far greater problem in
immunocompromised patients in whom the reactivation occurs
earlier in life and multiple attacks occur as well as complications
Ø Complications are rare and include encephalitis and disseminated
herpes zoster
Shingl

17. Laboratory diagnosis
. Direct Microscopy
2. Virus isolation
3. PCR
4. Serology
Treatment
Acyclovir and vidarabine are effective in the treatment of severe
varicella and zoster

18. Cytomegalovirus
• Belong to the betaherpesvirus subfamily of herpesviruses
• Double stranded DNA enveloped virus and 150-200 nm in size
• The virus exhibits strict host-specificity
• Cytomegalovirus infections are almost always inapparent, leading
to prolonged latency, with occasional reactivation
• Cytomegalovirus disease is rare but infection with the virus is
extremely common

19. Pathogenesis
Mode of
transmission
• The virus may be transmitted from person to person in several
ways (in utero, perinatally, or postnatally)
• Perinatal infection is acquired mainly through infected genital
secretions, or breast milk. Overall, 2 - 10% of infants are
infected by the age of 6 months worldwide. Perinatal infection is
thought to be 10 times more common than congenital infection
• Postnatal infection mainly occurs through
saliva. sexual and blood

20. • Initial replication of the virus occurs in the epithelial cells of
the respiratory and GI tracts which is followed by viraemia
resulting in infections of all organs of the body
• In symptomatic cases, renal tubular epithelium, liver and
CNS are also affected
• The virus establishes lifelong latent infection in monocytes,
B lymphocytes, epithelial cells and stromal cells of bone
marrow and in some organs like kidneys and heart
• Once infected, the virus remains in the person for life and
may be reactivated from time to time, especially in
immunocompromised individuals

21. Laboratory diagnosis
Specimens
Demonstration of
Cytomegalic cells
Isolation of
virus
Antigen detection
PCR
Serology
CMV-specific IgM can be detected in the serum by ELISA

22. Treatment
For treatment of severe CMV infections, ganciclovir is the drug of
choice
Prophylaxis
Ø Indicated only in high risk cases such as organ transplants,
premature infants, immunodeficient persons
Ø Screening of blood and organ donors
Ø Administration of CMV immunoglobulins and Acyclovir
Ø No vaccine is available

23. Epstein-Barr virus
ü Belong to the gammaherpesvirus subfamily of herpesviruses
ü EBV has affinity for lymphoid tissue. The B lymphocytes of
human beings have receptors (CD21 molecules) for EBV
ü EBV infected B lymphocytes are transformed in such a way that
they multiply continuously

24. Pathogenesis
Source of infection
Saliva of infected persons
Mode of transmission
Intimate oral contact, as in kissing appears to be main mode of
transmission

25. Ø The virus enters the pharyngeal epithelial cell through CD21 (or
CR2) receptors
Ø It multiplies locally, enters the blood stream and infects
B lymphocytes
Ø In most cases, the virus remains latent inside the lymphocytes,
which become transformed
Ø The activated B lymphoblast, along with the antigen of EBV,
matures into a long-lived memory lymphocyte in the germinal
centre of the lymph node
Ø This leads to polyclonal activation of the infected B lymphocytes
resulting in production of many kinds of antibodies to many
antigens
-accompanied by nonspecific increase in total IgM, IgG and IgA

26. Clinical manifestations
ü Most EBV infections are inapparent
ü Once infected, the virus is present in the individual for life
ü The following clinical manifestations may result from EBV
infection
1. Infectious mononucleosis
2. Infections in immunocompromised hosts
3. EBV-associated malignancies

27. Infectious Mononucleosis (Glandular fever)
It is an acute self-limiting disease of children and young adults
characterised by fever, sore throat, lymphadenopathy and
splenomegaly
In some patients jaundice may be seen which is due to hepatitis
Abnormal lymphocytes are present in the blood
The incubation period is 4-7 weeks and infection is believed to
occur through respiratory route by close contact with patients
Complications occur rarely but may be serious e.g. splenic rupture,
meningoencephalitis, and pharyngeal obstruction

28. EBV-associated malignancies
a) Burkitt’s lymphoma
b. Nasopharyngeal
carcinoma
c. B-cell lymphoma
Burkitt’s lymphoma
affecting jaw
Burkitt's lymphoma
showing disruption of
teeth and partial
obstruction of airway

29. Laboratory diagnosis
1. White blood cell count
2. Paul-Bunnell test
3. EBV – specific
antibodies
4. Antigen detection
5 Nucleic acid hybridisation
6 .PCR

30. Human Herpesvirus 6
ü HHV – 6 infects dividing CD4+ T lymphocytes
ü Saliva is the main route of transmission
ü Most HHV – 6 infections appear to be asymptomatic
ü They may, however cause exanthem subitum or roseola infantum
and infectious mononucleosis – like disease with cervical
lymphadenopathy
ü HHV – 6 can be isolated from peripheral blood mononuclear cells
in early febrile stage of the illness by co – cultivation
with lymphocytes

31. ü Primary HHV-6 or HHV-7 infection is associated with Roseola
Infantum, which is a classical disease of childhood
ü Most cases occur in infants between the ages of 4 months and
two years
ü A spiking fever develops over a period of 2 days followed by
a mild rash
ü The fever is high enough to cause febrile convulsions
ü There are reports that the disease may be complicated by
encephalitis
Roseola infantum

32. q Human Herpesvirus 8 is associated with Kaposi’s
sarcoma,
which is the commonest tumour in HIV infected individuals
Kaposi’s sarcoma

33. Thank you