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1. ROLE OF
HERPES VIRUSES IN
PERIODONTAL DISEASE
DR. DEEPALAKSHMI

2. HERPES VIRUS
 The most important enveloped DNA
viruses in oral pathology.
 Characterised by establishing latent
infections, persists indefinitely within
infected host and undergo periodic
reactivation
 Contracted in childhood or early adulthood
saliva ,blood or genital secretions.
 Hallmark of Herpes Virus infection is
immune impairment.

3. DESCRIPTION OF HERPES
VIRUS
 Typical Virion consists of an icosahedral
capsid assembly of 162 capsomers
enclosed in viral envelope.
 Genome is single double stranded DNA
molecule ranging size from 120 to 250
Kilobase pairs.
 Enveloped Virus
 Exhibits tissue tropism (neurotropic)
 Belongs to Herpetoviridae family

4. HERPES VIRUS
 Herpes virus form Cowdry type A
intranuclear(Lipschutz bodies) inclusion
bodies.They are of variable size and
granular in appearance.They do not
appear until virus replication.
 The viral productive phase followed by
latent phase in host cells.

5. HERPES VIRUS STRUCTURE

6. CLASSIFICATION OF HERPES
VIRUS
Eight types - based on biological and
clinical characteristics
 HSV-1
 HSV-2
 VZV
 HCMV
 EBV
 HHV-6
 HHV-7
 HHV-8

7. PATHOGENICITY OF VIRUS
Alpha subfamily
 HSV – 1
 HSV – 2
 VZV
 Characteristics:
- Short reproductive cycle
- Rapid lysis of infected cells
- Induces vesiculous lesion in
mucosa

8. PATHOGENICITY OF VIRUS
Beta subfamily
 HCMV
 HHV – 6
 HHV – 7
 Characteristics:
- Long reproductive cycle
- Slowly progressing infection
- Enlargement of infective cells
(cytomegalia)

9. PATHOGENICITY OF VIRUS
Gamma subfamily
 EBV
 HHV – 8
 Characteristics:
- Cytocidal for epithelial cells &
fibroblasts
- Specific for B lymphocytes, T
lymphocytes

10. HERPES SIMPLEX VIRUS -1
HSV isolated from patients with oral
lesions
were found to survive for as long as
 2 hours on skin,
 3 hours on cloth,
 4 hours on plastic.

11. HSV INFECTIONS
 Clinical manifestations are
determined by portal of entry, immune
status of the host, and whether the
infection is primary or recurrent.
 HSV is a neurotropic virus that infects
sensory ganglia, hence pain is a
common manifestation of mucocu-
taneous HSV infections.

12. HERPES VIRUSES 1&2
 Alphaherpesvirus subfamily
 Primary target cells are mucoepithelial cells
 Latency in neurons
 Man is the only natural host for HSV
 Spread in close contacts.
 Disseminated, spread toTRIGEMINAL
GANGLION (HSV-1) ,SACRAL GANGLION
(HSV-2)

13. CLINICAL MANIFESTATIONS

14. ACUTE HERPETIC
GINGIVOSTOMATITIS
 The commonest
manifestation of
primary
herpetic infection
 1 - 8 mm ulcers
with
necrotic bases are
present

15.  In infants and children younger than 6
years and also in adults
 Diffuse, erythematous enlargement of
gingiva characterised by presence of
discrete spherical gray vesicles which
rupture and form painful ulcers
accompanied by fever and
submandibular lymphadenopathy.
Duration : 7 – 10 days
ACUTE HERPETIC
GINGIVOSTOMATITIS

16. ACUTE HERPETIC
GINGIVOSTOMATITIS
 Communicable
 Diagnosis :
 Viral culturing
 Cytologic smear and biopsies
 Management
 Palliative, - copious fluid in take, soft diet,
analgesic, anasthetic mouthrinse and antipyretics.
 Systemic administration of acyclovir may be
beneficial

17. HERPES LABIALIS
 Herpes labialis (cold sore) is a
recurrence of oral HSV
 Prodrome of tingling,
or itching at the site
 About 12 hours later, redness
appears followed by papules
and vesicles
 45% of orally infected
individuals will experience
reactivation.

18. HERPETIC WHITLOW
Herpetic infection of a
dentists finger .Auto
inoculation of herpes
simplex virus from primary
site of infection to most
commonly the distal phalanx
of the fingers.
Occupational hazard for
health care workers not
wearing protective gloves.

19. HSV INFECTIONS
 Herpes Keratitis
 Herpes Retinitis
 Neonatal Herpes
 Herpes Gladiatorium
 Erythema Multifome
 Eczema Herpeticum
 Disseminated Herpes
 Bells Palsy

20. PUTATIVE ASSOCIATIONS
 Infectious agents have been implicated in the
pathogenesis of SCHIZOPHRENIA
 Herpes simplex virus (HSV) has been suggested as
a putative cause of schizophrenia based on its
tropism for the nervous system and epidemiological
studies linking herpes infection in pregnancy with
schizophrenia.
 Yolken R, Viruses and schizophrenia: a focus on
herpes simplex virus. Herpes 2004; 11:83A

21. VARICELLA ZOSTER VIRUS
VZV Causes:
 Varicella (chicken pox) primary
infection
of children
 Highly infectious disease transmitted
by
inhalation of infective droplets or by
direct contact
 Shingles(adults)

22. LATENCY IN VARICELLA
At the onset of rash, the virus may
spread from the skin along
the sensory nerves that supply the
skin to the dorsal root nerve
ganglia close to the spinal cord

23. HERPES ZOSTER (SHINGLES)
 Mainly affect a single
dermatome of the skin
 Vast majority of patients are
more than 50 years of age
 The latent virus reactivates in
a sensory ganglion and tracks
down the segment
 Vesicles in the dermatome
accompanied by intensive
pain which may last for
months (postherpetic
neuralgia)

24. EPSTEIN-BARR VIRUS
HHV - 3

25. EPSTEIN-BARR VIRUS
 Infects and replicates in oral and
oropharayngeal epithelium and in B-
lymphocytes
 Blood or saliva transmits EBV
 EBV infects most children before the
age of 2 years usually asymtomatic

26. CLINICAL MANIFESTATIONS
1. Infectious Mononucleosis . glandular fever
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. Hairy oral leukoplakia in AIDS patients
8. Chronic interstitial pneumonitis in AIDS patients.

27. EPSTEIN-BARR VIRUS
Cont.
TWO TYPES
1. EBV-1 predominates in western
hemisphere
2. EBV-2 predominates in Africa, HIV
infected individuals

28. ORAL HAIRY LEUKOPLAKIA
White lesion, usually
present on lateral
borders of tongue,
Vertically corrugated
hyperkeratotic patches

29. BURKITTS LYMPHOMA
 occurs in children
aged 3-14 years.
 respond favorably to
chemotherapy.
 It is restricted to
areas with
holoendemic
malaria. Therefore it
appears that malaria
infection is a
cofactor.

30. HUMAN CYTOMEGALOVIRUS
(HHV-5)
 Betaherpesvirus subfamily
 Primary target cells . monocyte, lymphocyte
& epithelial cells
 Site of latency . monocyte, lymphocyte, bone
marrow
 Spread . close contacts, transfusion,
transplantation, congenital

31. CMV TRANSMISSION
 Intrauterine
 most common congenital infection
 Perinatal
 Postnatal
 infants, parents of young infants,
daycare workers,
 hospital workers

32. CMV TRANSMISSION
Most common route of mother-to-baby
transmission is via
 Breast feeding
 Blood transfusion
 prevented by using blood from CMV
seronegative donors or cotton wool filtered
blood (removes WBCs & platelets)
 Organ transplantation

33. PUTATIVE ASSOCIATIONS
 ATHEROSCLEROSIS is an inflammatory
disease.Infection is a candidate
inflammatory trigger
 Epidemiological studies link CMV infection
with clinically manifest atherosclerotic
disease
 CMV antigen and nucleic acid sequences
in arterial smooth muscle cells of humans
suggests that viral infection of the arterial
wall may be common in the general
population

34. CMV PREVENTION
 Hand washing (1-30% of hospitalized
patients and 100% of infected infants shed
in urine and/or saliva)
 Use of CMV seronegative blood products
 Use of CMV seronegative organ donors
(impractical)
 Antiviral prophylaxis
 CMV immune globulin
 Vaccines

35. HUMAN HERPES VIRUS 6&7
 Roseola
infantum
 Sixth disease
 Exanthema
subitum

36. PATHOGENESIS
 HHV-6 and HHV-7 are ubiquitous and are
found worldwide.
 They are 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.
 By the time of adulthood, 90-99% of the
population had been infected by both
viruses.

37. HUMAN HERPES VIRUS 6
 HHV – 6 occurs in Gingiva of periodontitis
lesions
 Disease Association
 Roseola infantum – self limiting condition
showing mild skin exanthema and fever.
 Meningitis
 Mononucleosis not associated with EBV or
HCMV
 Multiple sclerosis
 Oral squamous carcinoma

38. HUMAN HERPES VIRUS – 7
 Detected in inflamed gingiva
 Disease association
Pityriasis rosea – a self limiting exanthema
characterised by crops of maculo papular
cutaneous lesions which may last for up to 2
weeks.Lesions of tongue and cheek reported
 Exanthema subitum

39. HUMAN HERPES VIRUS - 8
 Latency in B lymphocytes and
macrophages
 HHV-8 is the principle pathogen
with HIV infection constituting the
cofactor in the pathogenesis of
Kaposi sarcoma.
HHV-8 does not have an ubiquitous
distribution

40. HUMAN HERPES VIRUS -8

41. ASSOCIATION BETWEEN HERPES VIRUS
& PERIODONTAL DISEASE
 Rarely deducted in specimens from
healthy gingiva, present in all gingival
specimens from chronic periodontitis
lesions
 HSV, EBV, HCMV and HHV – 7 showed
significant associations with periodontitis
 HHV – 8 was detected only in gingival
specimens from HIV infected patients

42. ASSOCIATION BETWEEN HERPES VIRUS
& PERIODONTAL DISEASE
 Studies revealed close relationships between
EBV-1, HCMV and chronic periodontitis,
localised and generalised aggressive
periodontitis, Papillon – Lefevre syndrome
periodontitis and ANUG
 In adults periodontitis lesions HSV, HCMV
infects T-Lymphocytes and macrophages
and EBV-1 infects B-lymphocytes.

43. ASSOCIATION BETWEEN HERPES VIRUS
& PERIODONTAL DISEASE
 Erlich 1973 showed the presence of HSV
in sulcular epithelium of clinically healthy
gingiva, hence crevicular epithelium seems
to be the preferential site for latent Herpes
 Hochman.N, Ranes Y’1981studied the
presence of antibodies to HSV in GCF
using immunoflourescent method and
study showed the 84% of individual were
positive for antibodies to HSV

44. ASSOCIATION BETWEEN HERPES VIRUS
& PERIODONTAL DISEASE
Parra B, Slots.J’1996 34
 Demonstrated that human viruses may
occur in periodontitis lesion with relatively
high prevalence. Viral identification in
crevicular fluid was done using
polymerase chain reaction technique and
infected individual revealed HCMV

45. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
Contreras,A, Slots, J’19967
 Aimed to determine the frequency of
HCMV, EBV, HSV and HIV in subgingival
sample from periodontitis site
 Most frequent viruses detected from deep
periodontal pockets were HCMV and from
shallow pockets were EBV
 Viral co-infection occurred frequently in
deep periodontal pockets

46. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
 Preuset al (JCP 1987;14) hypothesized that
active periodontal HCMV infection initiates
overgrowth of subgingival
A.actinomycetemcomitans resulting in periodontal
breakdown.
 Preuset al ( JCP 1987 ;14)identified HCMV,
EBV,HSV, and HHV-7 in actively progressive
lesion in Papillon Lefevre syndrome periodontitis
 Contreras et al(Oral Microbiol Immunol 1997;12)
proposed that herpes virus together with
malnutrition and pathogenic periodontal bacteria's
are important determinants in development of
ANUG in Nigerian children

47. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
Velazco et al (JCP 1999 ;26:) studied
an 11 year old girl exhibiting Papillon –
Lefevre syndrome, including
hyperkeratosis, Palmo-plantaris and
severe periodontitis resembling LJP
revealed subgingival EBV and HCMV
and A.actinomycetocomitans.

48. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
 Ting.M’2000 44 showed the occurrence of
periodontal EBV and HCMV in LJP patients
aged 10 – 23 years
 Ronderos et al (J Periodontol) confirmed the
strong association between HCMV and Juvenile
periodontitis in a study of adolescents from
Jamaica. All LJP sample revealed HCMV
activation originated from sites showing absence
of radiographic crestal alveolar lamina dura, a
feature associated with progressive periodontal
disease. HCMV activation harboured relatively
high level of A.actinomycetocomitans.

49. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
 Saygun I, Sahin s’ 2002 37 conducted a
study to determine occurrence of HCMV,
EBV, HSV and its relation with clinical
parameters (pocket clinical depth and
clinical attachment loss) which was
statiscally significant.
 Yapar M.Saygun I ‘2003 30 evaluated
subgingival presence of HCMV and EBV in
patients with aggressive periodontitis and
healthy subjects and examined the effect of
treatment on these viruses 3 months
following surgery.

50. ASSOCIATION BETWEEN HERPES
VIRUS & PERIODONTAL DISEASE
 Ling LJ, HOCC’2004 29 demonstrated that
HSV is related to the severity of periodontal
diseases in terms of clinical attachment loss
 Kubar A 2005 28 evaluated that HCMV Counts
in aggressive periodontitis and EBV counts in
chronic periodontitis were positively correlated
with PPD and Probing attachment loss.

51. PATHOGENESIS
 Herpes Viruses causes periodontal
destruction
 Direct viral infection and replication
 Virally induced damage to host defense
 Mechanisms
 Direct cytopathic effects on fibroblasts,
keratinocytes, endothelial cells or
inflammatory cells
 It impairs the cells involved in host defense
and pre-disposing the host to microbial
super infection.

52. PATHOGENESIS
 It promotes subgivgival attachment and
colonisation of periodontopathic bacteria
 It alters the inflamatory mediators and
cytokine responses
 Produces tissue injury as a result of
immunopathologic responses to viral
infected cells.
 Eight known human herpes viruses,
HCMV, EBV-1 AND HSV are most
commonly detected in chronic and
aggressive periodontitis.

53. MODEL FOR HERPES VIRUS MEDIATED
PERIODONTAL DISEASE
Over growth of P.gingivalis /
A.actinomycetocomitans
Destructuve periodontal diseases
Bacterial plaque
Healthy Gingiva
Gingivitis
Herpes virus activation
Periodontopathic property
Cytokines Immuno suppression Cytoxicity
Inflammation /
Bone resorption /
Collagen destruction
HIV infected /
nutritionally stressed
tissue necrosis

54. LABORATORY DIAGNOSIS
1.Direct Detection - Electron microscopy of vesicle fluid -
rapid result.
Tzanck smear-Tzanck cells and Cowdry type A inclusion
bodies.
2.Immuno fluorescence of skin scrappings - can
distinguish between HSV and VZV
3.P CR - now used routinely for the diagnosis
4.Virus Isolation - HSV-1 and HSV-2 are among the easiest
viruses to cultivate.
5.Serology - Not that useful in the acute phase.

55. TREATMENT
 Acyclovir and Valacyclovir
 Penciclovir and Famciclovir
 Foscarnet
 All are viral DNA polymerase
inhibitors
 For life threatening infections
intravenous acyclovir
recommended

56. HERPES INFECTIONS
MISCELLANEOUS THERAPIES
 Dimethyl sulfoxide (DMSO) * Tannic acid
 Blistex
 Potassium permangnate
 Gentian violet
 Silver nitrate
 Antibiotics
 Steroid creams
 Iodine
 Lithium
 Red wine

57. HERPES INFECTIONS
MISCELLANEOUS THERAPIES
 Phototherapy • Burn therapy
 (laser/N2) • Application of ice
 X-rays • Diet therapy
 Ginseng • Aloe vera extracts
 Various herbs • Benzoin
 Topical epinephrine • Hydrogen peroxide

58. CONCLUSION
 Understanding the role of Herpes Virus is
important for diagnosing, determining more
specific treatment and preventing the disease.
 Herpes Virus infection decrease the reistance of
periodontal tissue, permitting subgingival over
growth of periodontal pathogenic bacteria
P.gingivalis, P.intermedia and Treponema
denticola.
 Tissue tropism of Herpes Virus infection contribute
to localised pattern of tissue destruction in
periodontitis .

59. CONCLUSION
 Herpes Virus reactivation in periodontal tissues
resulting in transient immunosuppression may
explain the episodic, progressive nature of human
periodontitis
 Herpes Virus may also interfere with periodontal
healing. A study of GTR showed that periodontal
sites harbouring EBV or HCMV had an average
gain of clinical attachment of 2.33 mm compared
with virally negative sites showed a clinical
attachment gain of 5.00 mm

60. CONCLUSION
 Herpes Virus may reduce the regenerating
potential of periodontal ligament.
 Vaccination against Herpes Viruses would
contribute an attractive approach in
periodontal prophylaxis and treatment.