Herpes viruses

power point presentation

1. HERPES VIRIDAEHERPES VIRIDAE
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Prevalent as early as ancient Greek times.
Hippocrates described the cutaneous spreading
of lesions. Shakespeare is thought to have been
familiar with these lesions and their transmission
and mentioned in his Romeo and Juliet. In 1893
Vidal recognized the human transmission of HSV
infection from one individual to another.
In 1919, Lowenstein confirmed experimentally the
infectious nature of HSV. In 1920's and 1930's,
the natural history and range of infections of HSV
were studied. By the 1940's and 1950's, research
established on diseases caused by HSV.

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The members of this family are
also known as herpesviruses.
Name is derived from the Greek
word herpein ("to creep or
crawl"). Latent, reactivation ,
recurring and lytic infections
are typical of this group of
viruses.
Herpesviridae, a large family of DNA
viruses that cause diseases in animals and
humans.

3. Medically important viruses – Three subfamilies.Medically important viruses – Three subfamilies.
3.3.Alpha herpes virinae.Alpha herpes virinae.
•Rapid growth,Rapid growth,
Latent infection in sensory ganglia.Latent infection in sensory ganglia.
HSV – 1, HSV – 2, V – Z Virus.HSV – 1, HSV – 2, V – Z Virus.
•Beta herpes virinaeBeta herpes virinae
Slow growth.Slow growth.
Grow best in Fibroblasts. Grow best in Fibroblasts.
Latent infection in salivary gland.Latent infection in salivary gland.
HHV – 5 ( CMV ) HHV– 6 , HHV – 7HHV – 5 ( CMV ) HHV– 6 , HHV – 7

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4. •Gamma herpes virinaeGamma herpes virinae
Grow in Lymphoblastoid cells.Grow in Lymphoblastoid cells.
Latent infection in Lymphoid tissue.Latent infection in Lymphoid tissue.
HHV – 4 (Epstein – Barr Virus)HHV – 4 (Epstein – Barr Virus)
HHV – 8 ( Kaposi’s sarcoma herpes virus)HHV – 8 ( Kaposi’s sarcoma herpes virus)

Neurotropic viruses: HSV,VZV; Lymphotropic viruses: EBV,HHV6,HHV7
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5. Morphology
•Enveloped (Lipid)
•Double stranded DNA
•Icosahedral capsid
•“Tegument”
•Glycoprotein spikes
( Surface spikes)
Naked virus
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6. •Virus replicates in host cell Virus replicates in host cell nucleus.nucleus.
•Cowdry type ACowdry type A intranuclear inclusion intranuclear inclusion
bodies.bodies.
•Susceptible toSusceptible to Ether Ether
ChloroformChloroform
Bile salts.Bile salts.
Heat labile.Heat labile.
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Replication and susceptibility

7. 1.Continuous cell line cultures.1.Continuous cell line cultures.
Monkey or Rabbit Monkey or Rabbit
kidney.kidney.
Human amnion cell line Human amnion cell line
cultures.cultures.
HeLa cell cultures.HeLa cell cultures.
Cytopathic effects :Cytopathic effects :
Well defined foci with heaped Well defined foci with heaped
up cells & syncitial formation.up cells & syncitial formation.

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8. 22.Growth on Chick embryo CAM.Growth on Chick embryo CAM
Shiny, non necrotic pocks.Shiny, non necrotic pocks.
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9. PathogenesisPathogenesis
Enters ‘thru’ defects in skin &mucus Enters ‘thru’ defects in skin &mucus membranes.membranes.
Local multiplication Local LN involvement.Local multiplication Local LN involvement.
Retrograde Retrograde axonal flow axonal flow from sensory nervesfrom sensory nerves …. Reaches Ganglia. …. Reaches Ganglia.
Maintains latencyMaintains latency
Viral replication in the nerves.Viral replication in the nerves.
Decreased CMI.Decreased CMI.
Centrifugal migration to skin & mucus Centrifugal migration to skin & mucus membranes.membranes.
Recurrence of the disease.Recurrence of the disease.
Physical, Emotional stress.
Trauma,
Fever.
Sun light.
Trigeminal, Sacral
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10. Primary infectionPrimary infection
Vesicle formationVesicle formation
(Ballooning degeneration of intra-epithelial cells)(Ballooning degeneration of intra-epithelial cells)
Site of eruption showsSite of eruption shows
Pain, tingling, warmth & itch, Pain, tingling, warmth & itch,
erythema & papule erythema & papule Thin walledThin walled
umbilicated vesicleumbilicated vesicle roof roof
breaks down and forms an ulcer.breaks down and forms an ulcer.
with fever (cold sore or fever blisters).with fever (cold sore or fever blisters).
Mucus membrane, non-keratinized Mucus membrane, non-keratinized
epithelia.epithelia.
Recurrent infections are seen with Recurrent infections are seen with severe severe
pain, ulceration.pain, ulceration.
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11. • Neuroinvasiveness
• Neurotoxicity
• Latency in dorsal root ganglion of CNS
•Damaged epithelium is repaired by Natural

killer cells.
•Viral glycoproteins initiates the T-cell
activity which activate primed B cells to
produce antibodies.
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12. 1. Mucocutaneous infections 1. Mucocutaneous infections
Cheeks, chin, forehead.Cheeks, chin, forehead.
Napkin rash in infants.Napkin rash in infants.
Acute gingivostomatitisAcute gingivostomatitis
Around the mouth & on lips.Around the mouth & on lips.
Pre-school children.Pre-school children.
Majority of primary infections;
Teething / oral thrush. / oral thrush.
Pathological lesions
Herpetic gingivostomatitis
Ruptured lesions
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13. .
Herpetic lesions in oral cavity
Dental anomalies followed
by Herpes viral infections.
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14. Skin infections
Herpetic whitlow ,
•Toddlers,
•Dentists,
•Nurses,
Herpes gladiatorum
(Wrestlers)
•Painful, swollen,
grouped vesicles with pus.
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15. Eczema herpeticum
Severe form of Atopic eczema(Kaposi's
varicelliform eruption.)
Extensive ulceration.
Eye infections:
Branching/dendritic
corneal ulcer.
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16. Visceral HSV:
• Esophagitis
• Tracheobronchitis
• Pneumonitis
CNS: Sporadic, fatal encephalitis(HSV 1).
Seizures, Hemi paresis and paraesthesia
Congenital infections :
•Transplacental infection.
•Congenital malformations are rare.
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17. -Symptomatic infections with sores, -Symptomatic infections with sores,
fever and lymphadenopathy of fever and lymphadenopathy of genital genital
tracttract, heal within 2-4 weeks. , heal within 2-4 weeks.
-Patients may suffer with 4-5 -Patients may suffer with 4-5
outbreaks (recurrent) within a year. outbreaks (recurrent) within a year.
-Causes psychological distress. -Causes psychological distress.
-Infection during late pregnancy poses -Infection during late pregnancy poses
a greater risk of transmission to the a greater risk of transmission to the
baby. baby.
--Sacral radiculopathy common with
urinary retention.
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HSV- 2 transmitted by auto infection, sexual
/orogenital contact. Most infections are Most infections are
asymptomatic.asymptomatic.

18. Genital herpes
Shaft of the Penis
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Labial herpes
Perianal herpes

19. 2.Neonatal herpes2.Neonatal herpes
Localized to Skin , eyes, Localized to Skin , eyes,
mouth. Disseminated mouth. Disseminated
infection leads to Multi infection leads to Multi
organ involvement organ involvement
(Liver, Adrenals, Brain)(Liver, Adrenals, Brain)
Complication:Complication:
Neurological impairment.Neurological impairment.
3.Aseptic meningitis:3.Aseptic meningitis:
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20. 1. Smears
•Scrapings from
base of Vesicle
•CSF,
•Saliva.
2.Serum
-Primary infection.
-ELISA most useful.
-CFT.
Laboratory diagnosis
Microscopy:
Tzanck smear
1 % Aqu. sol. of Toludine blue.

Multinucleated giant cells
with faceted nuclei ,
ground glass chromatin.
(Tzanck cells)
Best : Giemsa, Papanicolou stain
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21. 3.Antigen detection : 3.Antigen detection : Fluorescent antibody , ELISAFluorescent antibody , ELISA
4.Viral isolation:4.Viral isolation:
Cell line culture – growth within 1 -3 days.Cell line culture – growth within 1 -3 days.
5.Molecular techniques: 5.Molecular techniques: PCR and DNA probes.PCR and DNA probes.
Treatment :Treatment : No cure.No cure.
Acyclovir :Acyclovir : Primary infection (< 72 hrs). Primary infection (< 72 hrs).
Reduce the recurrences.Reduce the recurrences.
Famciclovir:Famciclovir: For resistant cases. For resistant cases.
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22. Varicella-Zoster virus
Varicella
•Mildest childhood exanthemata
•Source: Patient
•Droplet nuclei from Respiratory tract
•Inhalation. Incubation period 7– 23 days
•Centripetal distribution.
•Macule  Papule  Vesicle Pustule Scab
•Vesicular rash surrounded by a ring (Trunk)
•Superficial “Drop of water”
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23. •Hemorrhagic & bullous.
Interstetial Pneumonia.
Postviral encephalitis.
Guillain- Barre syndrome.
•Recovery is spontaneous.
•Can cross placenta 
Neuromuscular disorders.
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Appears in crops, Profuse in adults

24. Lab. Diagnosis :
Same as HSV.
Specimens : Buccal / Cutaneous lesions
Prophylaxis :
V – Z immunoglobulins.
Live attenuated varicella vaccine.
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25. Old age (>60 years).Old age (>60 years).
Latent virus in Latent virus in dorsal root or dorsal root or
cranial nerve cranial nerve gangliaganglia
 Neuritic pain,Neuritic pain, ParasthesiaParasthesia for for
weeks / months. weeks / months.
Unilateral, painful eruption in Unilateral, painful eruption in
thoracic region.thoracic region.
Commonest sites:Commonest sites:
Areas innervated by spinal cord Areas innervated by spinal cord
segments D3 – L2 & Trigeminal segments D3 – L2 & Trigeminal
nerve.nerve.
Herpes Zoster (Creeping girdle)
Herpes zoster ophthalmicus.Herpes zoster ophthalmicus.
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26. Complications :Complications :
 LMN Paralysis.LMN Paralysis.
 Meningo-encephalitisMeningo-encephalitis
 Ramsay Hunt syndromeRamsay Hunt syndrome
Facial palsy + eruption on tympanic Facial palsy + eruption on tympanic
membrane & external auditory canalmembrane & external auditory canal
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27. Cytomegalovirus Cytomegalovirus (Salivary gland virus)(Salivary gland virus)
Infected cells : Cytomegaly Infected cells : Cytomegaly (Owl’s eye appearance)(Owl’s eye appearance)
Most of the infections are unapparent.Most of the infections are unapparent.
Commonest cause for Commonest cause for congenital defectscongenital defects..
Pathogenesis:Pathogenesis:
Latent infection : Mononuclear leucocytesLatent infection : Mononuclear leucocytes
(Monocytes, B -lymphocytes)(Monocytes, B -lymphocytes)
Secretary glandsSecretary glands
Kidney.Kidney.
Replication seen in Replication seen in ductal epithelial cells.ductal epithelial cells.
Excretion in body fluids, Milk & Urine.Excretion in body fluids, Milk & Urine.
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28. Modes of transmissionModes of transmission
Transplacental. Transplacental.
 Sexual contact.Sexual contact.
Blood and its products.Blood and its products.
Organ transplantation.Organ transplantation.
Urine, Saliva, Cervical secretions,Urine, Saliva, Cervical secretions,
semen, breast milk.semen, breast milk.
Perinatal & Postnatal infections:Perinatal & Postnatal infections:
Infected birth canal,Breast milk.Infected birth canal,Breast milk.
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29. 11..Transplacental route:Transplacental route:
Condition severe if infection occurs during first Condition severe if infection occurs during first
trimester of pregnancy.trimester of pregnancy.
Cytomegalic Inclusion disease of Newborn(10%)Cytomegalic Inclusion disease of Newborn(10%)
ccharacterised by varied type of clinical manifestationsharacterised by varied type of clinical manifestations..
HepatospleenomegalyHepatospleenomegaly
JaundiceJaundice
Thrombocytopenic purpuraThrombocytopenic purpura
Haemolytic anaemiaHaemolytic anaemia
MicrocephalyMicrocephaly
Cerebral calcifications.Cerebral calcifications.
Mental retardation.Mental retardation.
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30. IMN like disease:IMN like disease:
Young adults.Young adults.
Hepatitis, fever, atypical lymphocytosis.Hepatitis, fever, atypical lymphocytosis.
(No pharyngitis, no lymphadenopathy, (No pharyngitis, no lymphadenopathy,
Negative for heterophile antibody)Negative for heterophile antibody)
Respiratory tract infections:Respiratory tract infections:
Pneumonitis in infants.Pneumonitis in infants.
Immunocompromised individuals:Immunocompromised individuals:
PneumoniaPneumonia
Fatal encephalitisFatal encephalitis
ChorioretinitisChorioretinitis
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31. Lab. Diagnosis:Lab. Diagnosis:
Adults:Adults: Urine, Saliva, BAL, Urine, Saliva, BAL,
Semen & Cervical secretions.Semen & Cervical secretions.
Neonate:Neonate: Urine Urine
1. 1. Microscopy:Microscopy:
Centrifuged deposits of secretions.Centrifuged deposits of secretions.
Giemsa stain:Giemsa stain: Cytomegalic cells Cytomegalic cells
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32. 2.Isolation:2.Isolation:
““Human diploid fibroblast cell” culture.Human diploid fibroblast cell” culture.
Large retractile cells with cytoplasmic Large retractile cells with cytoplasmic
granules.granules.
3.Serology:3.Serology:
Anti CMV IgM Ab estimation by ELISA. Anti CMV IgM Ab estimation by ELISA.
Treatment:Treatment: Ganciclovir & Foscarnet. Ganciclovir & Foscarnet.
Prophylaxis:Prophylaxis: Acyclovir. Acyclovir.
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33. Epstein – Barr (EB) VirusEpstein – Barr (EB) Virus
Burkitt's lymphoma in 1964 .Burkitt's lymphoma in 1964 .
Affinity for B – lymphocytes (CD 21 Affinity for B – lymphocytes (CD 21
receptors.)receptors.)
80 – 90% of children by three years of age.80 – 90% of children by three years of age.
Asymptomatic.Asymptomatic.
Not highly contagious. Not highly contagious.
Droplets are not infectious.Droplets are not infectious.
Source :Source : Saliva, Oropharyngeal secretions Saliva, Oropharyngeal secretions
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34. Pathogenesis Pathogenesis
Infected saliva.Infected saliva.
Pharyngeal epithelial cells (Multiplies locally).Pharyngeal epithelial cells (Multiplies locally). PersistencePersistence

Shed in salivaShed in saliva
Invades blood streamInvades blood stream
Infects B. lymphocytesInfects B. lymphocytes..
Liver Liver Spleen Spleen Polyclonal activationPolyclonal activation
cell deathcell death . .
Unchecked Unchecked replication results in results in LymphomasLymphomas
Neoantigen formationNeoantigen formation
Atypical Atypical lymphocytosis..
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35. Clinical DiseasesClinical Diseases
Incubation period : 4 – 7 weeksIncubation period : 4 – 7 weeks
1.Infectious Mononucleosis1.Infectious Mononucleosis
(Glandular disease, Kissing disease)(Glandular disease, Kissing disease)
Acute self limiting illness.Acute self limiting illness.
Fever, sore throat.Fever, sore throat.
Lymphadenopathy. Lymphadenopathy.
Sub clinical Hepatitis, Tender spleenomegalySub clinical Hepatitis, Tender spleenomegaly
Abnormal lymphocytes in PSAbnormal lymphocytes in PS
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36. 2.Chronic fatigue syndrome.
3.Malignancies associated with EB.
Burkitt’s lymphoma
(Malignant B cell lymphoma of jaw)
Nasopharyngeal carcinoma
Lymphomas in HIV infected
persons.
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37. Lab diagnosisLab diagnosis
1.Blood smear examination :1.Blood smear examination :Atypical Lymphocytosis.Atypical Lymphocytosis.
2.Paul - Bunnel test:2.Paul - Bunnel test:
Heterophile antibody detection test.Heterophile antibody detection test.
Inactivated serum + 1% sheep RBC Inactivated serum + 1% sheep RBC
suspension suspension  37 37
00
C C  4 hrs 4 hrs 
Agglutination (>100)Agglutination (>100)
3. EBV Specific antibodies:3. EBV Specific antibodies:
EBNA EBNA Ab EBNAAb EBNA
Ig M VCA,Ig M VCA,Ig G VCAIg G VCA
4. PCR:4. PCR: More sensitive. More sensitive.

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38. HHV – 6HHV – 6
Isolated in 1986 from AIDS patientIsolated in 1986 from AIDS patient
T - lymphocytotropic (CD+)T - lymphocytotropic (CD+)
Transmission through Oral secretions.Transmission through Oral secretions.
Roseola infantum (Exanthema subitum)Roseola infantum (Exanthema subitum)
High fever with generalized rash.High fever with generalized rash.
Chronic fatigue syndromeChronic fatigue syndrome..
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39. HHV – 7HHV – 7
Isolated from AIDS Isolated from AIDS
patient in 1990.patient in 1990.
No disease No disease
association.association.
Remains as orphanRemains as orphan
virus.virus.
HHV – 8HHV – 8
Kaposi's sarcoma related Kaposi's sarcoma related
herpes virus.herpes virus.
 In 1994 In 1994 : Association : Association
with with Kaposi's sarcomaKaposi's sarcoma..
(Rare type of “B cell (Rare type of “B cell
lymphoma” from lymphoma” from

AIDS patients).AIDS patients).
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40. 4040
Alzheimer's disease
atherosclerosis
cholangiocarcinoma
Crohn's disease
chronic fatigue syndrome
fibromyalgia
Irritable bowel syndrome
multiple sclerosis
pancreatic cancer
pityriasis rosea
Type II Diabetes
Research is currently ongoing into a
variety of side-effect or co-conditions
related to the herpesviruses.

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Prepared for e-learning by
Dr .P.SRINIVASULU REDDY , M D.,
Professor, Department of Microbiology
Narayana Medical College
NELLORE