VIRUSES IN PERIODONTAL

DISEASES

Presenter: Rahat Saleem

PG 3RD YEAR
Department of periodontology
 CONTENTS
• Introduction
• Virus classification
• Viral components and structure • Coronavirus & periodontal disease
• Replication of viruses • Coronavirus
• Human immunodeficiency virus • SARS-COV-2
• Structure • Pathogenesis
• Pathogenesis • Proposed mechanism and link
• Periodontal conditions between oral hygiene and covid-19
• Herpes Viruses in periodontal • Host response to viral infections
disease • Diagnostic aids
• Structure • Therapeutic implications
• Herpesviral–bacterial model of • Challenges for the viral hypothesis
periodontitis • Summary
• Evidence for the viral etiology • Conclusion
• References
 INTRODUCTION
• Virus is an infective agent that typically consists of a nucleic acid
molecule in a protein coat, is too small to be seen by light microscopy, and
is able to multiply only within the living cells of a host.

• Smallest living unit

• Viruses cause many acute and chronic diseases in humans.

• New viruses are continually being discovered and already known viruses are
being implicated in clinical conditions with previously unknown etiologies.

• Viruses occupy a unique position in biology. They are obligate intracellular

agents, which are metabolically and pathogenically inert outside the host
cell.
• The complete virus particle, called a virion, generally has a diameter of only
30–150 nm.

• Viruses are grouped into 3600 species, 71 families, and 164 genera. Fewer
than 40 viral families and genera are identified to be of medical importance
in humans.
• The etiopathogenesis of periodontal disease is a complex process
• Bacterial etiology alone has not been able to substantiate…

1. Rapid periodontal tissue breakdown with minimal plaque

2. Phase of disease activity & quiescence
3. Site specificity in periodontal disease
4. Progression to advanced periodontal destruction in a fraction of
given population

• Various HHVs have emerged as putative pathogens in destructive

periodontal disease
Slots et
al. 2006
• HHV-bacterial pathogen model Slots
et al 2007
EVOLUTION OF VIRUSES
 BACTERIA VIRUS
Intercellular organisms Intracellular organisms
Size Larger (1000nm) Smaller (20 - 400nm)
Opinions differ on whether viruses
Living Living organism are a form of life or organic
attributes structures that interact with living
organisms.
DNA and RNA floating freely DNA or RNA enclosed inside a coat
in cytoplasm. Has cell wall of protein.
Structures
and cell membrane.

Ribosomes Present Absent

Invades a host cell and takes over the

Fission- a form of asexual cell causing it to make copies of the
Reproduction reproduction viral DNA/RNA. Destroys the host
cell releasing new viruses.
Vaccines prevent the spread and
Antibiotics antiviral medications help to slow
Treatment
reproduction but can not stop it
completely.
 VIRAL NOMENCLATURE

• Picornavirus - pico + rna

• Papovavirus - papilloma , polyoma , vacuolating viruses

• Retrovirus - reverse – virus directed synthesis of DNA from RNA

template

• Poxviruses - symptoms caused by one of its members , smallpox

 VIRAL COMPONENTS AND STRUCTURE
• Virion –is a complete virus particle consisting of RNA or DNA
surrounded by a protein shell, constituting the infective form of virus
i. Genome - either DNA or RNA but not both
ii. Capsid
iii. Envelope
iv. Peplomers
v. Enzymes
 Classification of viruses
• THE TYPE OF THE NUCLEIC ACID GENOME (DNA OR RNA).
DNA viruses
•As their name implies, DNA viruses use DNA as their genetic material.
•Some common examples of DNA viruses are parvovirus, papillomavirus, and herpesvirus.
•DNA viruses can affect both humans and animals and can range from causing benign
symptoms to posing very serious health.

RNA viruses
•The virus that possesses RNA as genetic material are called RNA viruses.
•Rotavirus, polio virus, yellow fever virus, dengue virus, hepatitis C virus, measles
virus, rabies virus, influenza virus and Ebola virus are examples of RNA virus.

DNA-RNA viruses
• The RNA tumor viruses called Leukoviruses and Rous’s viruses unusually contain both
DNA and RNA as genetic material.
• The strandedness of the viral nucleic acid (single-stranded or double
stranded genome).
BALTIMORE CLASSIFICATION (1971)
 Classification of viruses
On the Basis of Presence of Envelope

•The envelope is a lipid-containing membrane that surrounds some virus particles. It is

acquired during viral maturation by a budding process through a cellular membrane
•Virus encoded glycoproteins are exposed on the surface of the envelope. These
projections are called peplomers.
Enveloped Virus
•DNA viruses: Herpesviruses, Poxviruses, Hepadnaviruses
•RNA viruses: Flavivirus, Toga virus, Coronavirus, Hepatitis D, Orthomyxovirus,
Paramyxovirus, Rhabdovirus, Bunyavirus, Filovirus
•Retroviruses

Non-Enveloped Virus
•DNA viruses- parvovirus, adenovirus and papovavirus.
•RNA viruses- Picornavirus, Hepatitis A virus and Hepatitis E virus
NON ENVELOPED VS ENVELOPE VIRUSES
VIRUS REPLICATION
HUMAN IMMUNODEFICIENCY VIRUS
• Retrovirus

• HIV 1

• HIV 2

• 1981 – first indication of AIDS in NY and LA

• 1983 – Luc Montagnier et al isolated retovirus and called it LAV –

lymphadenopathy associated virus

• 1984 – Robert Gallo – HTLV III – Human T cell lymphotropic virus III

• 1986 – International committee of Virus Nomenclature - HIV

STRUCTURE
 PATHOGENESIS
• Receptor for the virus is CD4
• Primary CD4+ - T lymphocytes (helper/inducer)
5-10% of B lymphocytes
10-20% of monocytes and macrophages
• Specific binding to CD4 receptor - envelope glycoprotein gp120.
• Cell fusion - transmembrane gp41.
• CXCR4 for T cell tropic HIV ,
CCR5 for macrophages –coreceptors
VIRUS ATTACHMENT AND PENETRATION
 PATHOGENIC MECHANISM
This damage is caused to CD4+ T cells.
T4 cells and T4:T8 ratio is reversed.
suppress function of infected cells
without causing structural
damage.
T4 cells do not release IL2, IFN, and
other lymphokines
•Helper T cell activity is essential for optimal B cell
HUMORAL function
MECHANISM •Hypergammaglobulinemia is more a hindrance than
help because of ‘USELESS Ig’ to irrelevant Ags and
also autoantibodies.

•Affected due to lack of secretion of activating

factors by T4 lymphocytes.
MONOCYTE – •So chemotaxis, antigen presentation and
MACROPHAGE FUNCTION intracellular killing is diminshed.
•Activity of NK cells and cytotoxic T cells is
affected
 LINEAR GINGIVAL ERYTHEMA

• A persistent , linear , easily bleeding, erythematous gingivitis

• Possible etiology – candida dubliniensis

• Prevalence in HIV patients – 0-49%

 NECROTISING ULCERATIVE GINGIVITIS
PERIODONTITIS , STOMATITIS
• NUG – destruction of 1 or more interdental papilla
, confined to marginal gingiva
• NUP- involves PDL and alveolar bone. Bone is exposed
– necrosis – sequestration
• NUS – extends past MGJ into mucosa and osseous
tissues
• Higher prevalence in HIV patients
• NUP – marker of immune deterioration with 95%
predictive value
• Prevalence of Chronic periodontitis – 5-69%
PROPOSED MODEL OF HIV REACTIVATION DURING
CO-INFECTION

HIV latently infecteted cells

Co infection
Activation of membrane receptors
by pathogens and cytokines

Turns on down stream signaling

pathways

Activation of transcription factors like

NF-kB

Activation of HIV LTR

proinflammatory genes transactivation

Production of
proinflammatory cytokine Production of new
virions
 HERPES VIRUSES
• Membership in the family herpesviridae is based on four layered structure
of virion.
 CLASSIFICATION

α
HSV1

HSV2
VZV

β γ
HCMV EBV
HHV8
HHV6

HHV7
VIRUS REPLICATION
MECHANISMS OF PERIODONTOPATHIC
POTENTIAL OF HERPES VIRUSES
1. Direct cytopathic effects

2. Impair cells involved in host defense

3. Promote subgingival attachment and colonization

4. Altered Inflammatory mediator

5. Reducing the cell surface expression of MHC class I molecules

 HERPES SIMPLEX VIRUSES

• HSV1,2 - usually affect skin and mucosa

• HSV1- shed principally in saliva- Orofacial Infections

• HSV2- transmitted sexually- genital infection

• Primary infection - childhood.

• At sites of epithelial infection - viral Ags induce cell mediated

immunity which is the key of recovery and latency.
• Primary herpetic gingival disease of viral origin is one of the most common
infection(Kuzushima 1991)
• Asymptomatic in childhood.
• Clinical features- gingivitis, vesicles that leave ulcerations,
lymphadenopathy and fever.
• Healing - 10-14 days.
• Recurrence - mucocutaneous junction of lips,palate or gingiva (recurrent
herpetic gingivostomatitis).
 VARICELLA ZOSTER VIRUS
• Varicella (chickenpox) - childhood

• Herpes zoster- aged and immunocompromised

• Enters by inhalation - replicates in mucosa of respiratory tract.

• Dissemination - bloodstream and lymphactics.

• Virus multiplies in mononuclear leukocytes and capillary endothelial cells.

 VARICELLA
• Occurs during first 5-10 years of life.
• Vesicles and ulcers first appear in mouth on palate, tongue, gingiva followed by
cutaneous rash that spreads centrifugally from head and trunk.
• Oral lesions-painful
• Cutaneous lesions-painless but itchy and lead to secondary
infection and permanent scars
 HERPES ZOSTER
• Herpes zoster- from reactivation of virus that remain latent in sensory ganglia.
• Lesions similar to varicella but remain confined to single dermatome and
are unilateral.

• Intraorally lesions found if 2nd and 3rd branch of trigeminal nerve is involved,
which may lead to alveolar bone necrosis.
 EPSTEIN BARR VIRUS
• Transmitted by oral secretions or blood.
• Virus replicates in epithelial cells or B cells of oropharynx.
• All seropositive patients-actively shed virus in saliva.
• Resting memory B cells –main site of persistence of EBV.
• EBV infection - in children is subclinical,
in adults-infectious mononucleosis.
• Symtoms of infectious mononucleosis- fever, lymphadenopathy, pharyngitis,
oral ulcers, palatal petechiae, less commonly gingival ulcerations
Oral hairy leukoplakia
• Main lesion of EBV .
• Non malignant hyperpalstic lesion of epithelial cells which shows
noncytolytic EBV replication.
• OHL-appears as white corrugated lesion on ventral –lateral aspect of tongue and
may be unilateral/bilateral.
 HUMAN CYTOMEGALOVIRUS
• Most common cause of congenital and perinatal infections.

• Infants infected through placenta, during delivery or breast feeding.

• Infects epithelial cells, endothelial cells, smooth muscle cells,

mesenchymal, hepatocytes, granulocytes, macrophages.

• Found in saliva, urine, semen, breast milk.

• In HIV infected patient-oral ulcers as well as gingival

hyperplasia is noted.
HERPESVIRAL–BACTERIAL MODEL OF PERIODONTITIS
 HERPESVIRUS : AN ETIOLOGIC FACTOR
FOR PERIODONTAL DISEASE?

1. Virus detection in gingival tissue

• Cultured epithelial cells and fibroblasts – healthy gingiva – susceptible to HSV

infection – may act as reservoir of latent virus - Zakay 1982

• Indirect immunofluroscence assay – HSV 1 Ag detected in PD diseased

patient’s gingival biopsies - Ehrlich et al 1983

• HSV Ag – healthy gingiva - Amit et al 1992

• HSV DNA in intact gingival cells – virus present in latent state

• In periodontitis patient by using nested PCR –

i. Monocytes and macrophages - HCMV , HSV

ii. T cells – HCMV , HSV

iii. B cells - EBV

2) Higher frequency of virus detection in the gingival tissue of periodontitis sites
than in healthy sites
• In 20 patients with periodontitis HCMV DNA – 13 biopsies, EBV DNA – 10
biopsies.
• HSV DNA-7 biopsies Healthy gingiva – HSV in1/3 -Contreras et al , 1999
• Herpes viral DNA in gingival tissues could be detected in periodontally healthy
or diseased subjects by nested PCR.
3. Higher frequency of herpes virus detection in GCF from periodontaly
diseased sites than from gingivitis/healthy sites
• Parra and Slots (1996)
– 78% of advanced periodontitis patients were positive for at least 1/5
– HCMV (60%) >EBV (30%)> HSV (20%) HPV (17%) and HIV
(7%).
– Only 31% of the gingivitis patients were virus positive

•89% of the patients yielded at least 1/5 (HCMV) deep pockets, whereas only
56% yielded viral DNA from shallow periodontal sites
4. Higher frequency of virus detection in subgingival plaque from periodontaly
diseased than from healthy sites

• Saygun et al 2002...

VIRUS CHRONIC HEALTHY

PERIODONTITIS
HCMV DNA 44 % 14.3%

EBV DNA 17 % 14.3%

HSV DNA 6.7% -

• Frequency of detection lower compared to previous studies

5. Detection of activated herpes virus in the GCF of periodontal lesions

Contreras & Slots 1998 –

• Reverse transcriptase-PCR to examine mRNA transcription of subgingival
HCMV.
• HCMV major capsid proteins - in deep periodontal pockets but
not in any shallow pocket
• Active HCMV replication could occur in periodontal sites

Croen et al 1991
• Several risk factors for periodontal disease – have potential to reactivate
Herpesvirus
6. Interaction of herpesviruses with periodontal pathogens

• The subgingival detection of EBV, HCMV could be associated with

an increased presence of periodontal pathogens(A.a ,P g)
Contreras et al 1991
• LJP – Aa associated with active HCMV infection
• HCMV , EBV , HSV along with Pg , D pneumosintes – active periodontitis
• And immunosuppressive properties of herpesvirus – overgrowth of
subgingival periodontal bacteria
• Their can be a bidirectional interaction between herpesviruses and
bacteria

• Bacterial enzymes or other inflammation-inducing factors have the

potential to activate periodontal herpesviruses

• In addition ,P. gingivalis suppress the interferon-gamma antiviral

host response

• Herpesvirus infection predisposes periodontal tissue to the bacterial

superinfection
 CORONAVIRUS
• Coronaviruses belong to the Coronaviridae family in the Nidovirales
order.
• Corona represents crown-like spikes on the outer surface of the virus.
• Coronaviruses are minute in size (65-125 nm in diameter) and contain a
single-stranded RNA as nucleic material.
• The subgroups of the coronavirus family are alpha (α), beta (β), gamma
(γ), and delta (δ)
• α- and β-CoV are able to infect mammals, while γ- and δ-CoV tend to
infect birds.
 SARS-COV 2
• The SARS-CoV-2 is a β-coronavirus, which is enveloped non-segmented positive-
sense RNA virus.

• Previously, six CoVs have been identified as human-susceptible virus, among which
α-CoVs HCoV-229E and HCoV-NL63, and β-CoVs,HCoV-HKU1 and HCoV-OC43
with low pathogenicity, cause mild respiratory symptoms similar to a common cold.

• The other two known β-CoVs, SARS-CoV and MERS-CoV lead to severe and
potentially fatal respiratory tract infections.
PATHOGENESIS
LINK B/W PERIODONTAL INFECTIONS
& CORONAVIRUS

• It is common for respiratory viral infections to predispose patients to bacterial

superinfections, leading to increased disease severity and mortality.
• Strands of the coronavirus have shown to enhance streptococcal adherence to
epithelial cells along the respiratory tract, causing complications such as
pneumonia and inflammatory damage in the lungs that inhibit the clearance of
bacteria.
• Severe infections leads to remarkably higher neutrophil count and a significantly
lower lymphocyte count which is common in bacterial infections.
 LINK B/W PERIODONTAL INFECTIONS
& CORONAVIRUS

Bacteria that colonise the mouth are shed into the saliva. The pathogenic bacteria
within the saliva can then be aspirated into the lower respiratory tract and cause or
aggravate an infection.
, Role of Oral Bacteria in Respiratory Infection, J Periodontol, 1999
LINK B/W PERIODONTAL INFECTIONS
& CORONAVIRUS

• Zheng et al(2020) suspected that, in severe cases of COVID-19, bacterial superinfection is

common.
• He stated that abnormally low levels of lymphocytes, which are usually the main line of
defense against viral infections, indicates either functional exhaustion of cells or bacterial
superinfection superseding the original viral infection.
• Also, Zhou et al.(2020) noted 50% of patients with severe COVID-19 died with the
presence of a secondary bacterial infection.
 Proposed mechanism to explain the potential role of oral
bacteria in the pathogenesis of a respiratory infection

Aspiration of oral pathogens into the lungs

Periodontal disease-associated enzymes may modify the mucosal surfaces to allow

for adhesion and colonization of respiratory pathogens

Periodontal disease-associated enzymes may destroy the salivary pellicles on bacteria

to hinder clearance from mucosal surfaces

Respiratory epithelium may be altered by periodontal-associated cytokines to

promote infection by respiratory pathogens.

Hayata M, Watanabe N, Tamura M. The Periodontopathic Bacterium Fusobacterium nucleatum Induced Proinflammatory Cytokine Production by
Human Respiratory Epithelial Cell Lines and in the Lower Respiratory Organs in Mice. Cell Physiol Biochem 2019; 53: 49–61.
• Gong et al (2020) found that patients with severe COVID-19
infections express systemic inflammation and significantly higher
levels of interleukin-6, interleukin-2, interleukin-10, TNF and C-
reactive protein.
• The main comorbidities associated with an increased risk of
complications and death from COVID-19 are also associated with
altered oral biofilms and periodontal disease, hence why the link
between poor oral health and COVID-1
• Periodontopathic bacteria is also present in the metagenome of
patients severely infected with SARS-CoV-2, where high reads for
Prevotella (493 reads), Staphylococcus (1,659 reads) and
Fusobacterium (463 reads) were discovered complications is
suggested.
• More researches are required to be performed on bacterial
superinfections, and the connection b/w the oral microbiome and
COVID-19 complications to establish the importance of oral
hygiene and pre-existing oral disease in the severity and mortality
risk of COVID-19.
 HOST RESPONSE
I. ANTIBODY MEDIATED ANTIVIRAL IMMUNITY
II. CELL MEDIATED ANTIVIRAL IMMUNITY
III. NON SPECIFIC FACTORS
 HOST RESPONSE
I] ANTIBODY MEDIATED ANTIVIRAL IMMUNITY

a) Viral Antibodies :
• IgG – block adsorption and penetration into host cells

• Enhance ingestion by PMN’s and macrophages

• Agglutinate the virus – reduce viral load

• Ag – Ab complex - increase size to trigger phagocytosis

b) Antibodies with activation of complement system
• Generation of C3 –viral Ab complex allows binding of C3
receptor – phagocytosis

• Ab and Complement – lysis of virus with envelope – damage

lipid membrane
- Lysis of infected cells
• Complement alone – activate alternate pathway – lysis or increased
phagocytosis of coated material

c) Ig bound to virus infected cell interacts with Fc receptor bearing

lymphocytes (K cells) – cell lysis
II] CELL MEDIATED ANTIVIRAL IMMUNITY
III] NON SPECIFIC FACTORS
1. Fever
2. Interferon Production
3. Natural Killer Cell Activity
 ACUTE INFECTIONS
• Events that contribute to cytopathic changes & cell death
1) Inhibition of host cell DNA , RNA and protein synthesis
2) Virion proteins
3) Activation of lysosomal enzymes
4) Inhibition of Na K pump
PERSISTENT INFECTIONS
 INTERFERON

• Innate mechanism

• Group of peptides – bind to receptors of neighbouring cells - resistant to

infection - limiting focus of infection

• Regulate cell differentiation and immune reactivity

• IFN α – T lymphocytes

• IFN β – virus stimulated fibroblasts

• IFN γ- most potent , Ag activated T cells

 Degrade
viral RNA
Cytotoxic
NK cell
T cell
activity
activity
1. synthesis of lysosomal enzymes

IF
2.Expression of receptors for Fc
Expressio
Effects on n of portion of Ig
adhesion
macropha proteins
3.Decreased migration of
ge macrophages – expression of

N Productio
MIF
4. Production of IL 1 , TNF alpha
APC n of
function cytotoxic – augment lymphocyte activation
Mitogenes factors 5.Contribute to T cell response -
is of B
enhance APC function of
cells
activated macrophagess
DIAGNOSTIC AIDS
• Traditional methods:
• Cell culture to detect characteristic cytopathic effects, morphologic
determination of intracytoplasmic and intranuclear inclusion bodies,
• Immunohistochemical techniques, immunoassays to identify viral
antigens in clinical specimens,
• or the measurement of total or class-specific antibodies against
specific viral antigens.
• In some viral infections, IgM antibodies are useful for determining
primary infection, and IgG antibodies for assessing the susceptibility
to primary infection and viral reactivation.
DIAGNOSTIC AIDS
• Recent techniques
• Viral nucleic acid can be measured directly by hybridization, or be detected after
amplification by nucleic acid amplification methods.
• Polymerase chain reaction (PCR)
• Microarray-based detection assay
THERAPEUTIC IMPLICATIONS
• Conventional periodontal therapy can reduce the periodontal load of herpesviruses.
• Mechanical debridement has suppressed subgingival Epstein– Barr virus to
undetectable levels in 12 of 21 patients, and has decreased subgingival Epstein–
Barr virus genome-copies by sixfold and subgingival cytomegalovirus genome-
copies by 38-fold. ( Saygun I, Kubar A, O¨ zdemir A, Slots J., J Periodontal Res 2005)
• After repeated debridement, 24 patients with periodontitis yielded no
cytomegalovirus, but were found to have Epstein–Barr virus and herpesvirus-7,
suggesting that cytomegalovirus is particularly susceptible to the effects of
periodontal therapy. (Rotola A, Cassai E, Farina R, Caselli E, Gentili V, Lazzarotto T, Trombelli L., J Clin Periodontol
2008)
THERAPEUTIC IMPLICATIONS
• Anti-herpesvirus chemotherapy can also decrease the salivary viral load.
• A short course of valacyclovir, 2 g twice on the day of treatment and 1 g twice the following
day, resulted in a significant decrease in the salivary occurrence of Epstein–Barr virus
compared with controls . (Miller CS, Avdiushko SA, Kryscio RJ, Danaher RJ, Jacob RJ. , J Clin Microbiol 2005)
• Valacyclovir, 500 mg orally twice daily for 1 month, given to elite male distance runners,
reduced the salivary load of Epstein–Barr virus by 82% compared with placebo.
• Valacyclovir therapy, 3 g per day for 14 days, resulted in a reduction, of more than 100-fold, of
Epstein–Barr virus genome-copies in oral wash fluid of patients with acute infectious
mononucleosis . (Cox AJ, Gleeson M, Pyne DB, Saunders PU, Clancy RL,Fricker PA., Med Sci Sports Exerc 2004)
• Chemotherapeutics are effective against viruses in the lytic phase, but not against viruses in the
latent phase, limiting their potential use to disease-active infections.
THERAPEUTIC IMPLICATIONS
• Patients infected with covid-19 treated with a combination of
hydroxychloroquine (antiviral) and azithromycin (antibiotic) was shown
to cure 100% of patients virologically after six days, compared to patients
who had hydroxychloroquine alone (57.1%) and those who had no
treatment (12.5%). (Gautret P, Lagier J-C, Parola P et al. Int J Antimicrob
Agents 2020) .
• Future management of periodontal diseases may benefit from anti- viral
immunotherapeutics: either prophylactic vaccines, which harness the
immune system of healthy subjects to prevent infection with disease-
causing viruses; or therapeutic vaccines, which stimulate the immune
system into combating existing viruses and disease.
CHALLENGES FOR THE VIRAL
HYPOTHESIS
1. Investigators

• Most clinical association studies have been carried out by the same group of
investigators

• Samples were analysed in the same laboratory

• Confirmation by other independent researchers is lacking

2. Method
• The nested PCR works with two primer pairs and two different amplification tests,
one after the other

• Display higher specificity& sensitivity

• It is very susceptible to contamination, and can produce false positive results

3. Sample population

• A higher frequency of co-infection and occurrence of EBV and HHV-6 has been
noted in HIV-positive

Contreras et al, 2001

• HIV status was not investigated

• The doubt remains whether the subjects included were true representative
4. Inferences of causality

• One difficulty directly relates to the sampling procedure in diseased sites

• Samples from diseased sites are more likely to contain viruses present in blood.
• Active HCMV replication has been demonstrated in periodontal sites

• The reactivation - periodontal disease activity,

• -just the opposite may be the case:

• -periodontal disease activity caused by bacterial infection - trigger virus

reactivation.
 SUMMARY
Disease Viruses active studies
Gingivitis • 20% for EBV & 33% for CMV Rotola A et al(2008)
• Herpes virus-infected periodontallyhealthy and gingivitis
sites typically harbour the viruses in a non- transcriptional
state
• Pregnancy might increase the risk of subgingival EBV Eres G et al (2011)
presence by 3.647 times
Periodontitis • HSV (13–100%), EBV (3–89%), & CMV (0.3–83%) Kubar et al (2005)
Imbronito et al (2008)
Bilichodmath et al (2009)
Aggressive • Cytomegalovirus and Porphyromonas gingivalis in sites Michalowicz BS et al(2000)
periodontitis with localized aggressive periodontitis.
• Cytomegalovirus transcription of major cuspid protein
detected in deep periodontal pockets of patients( 10–14 yrs
age). Saygun I et al(2004)
• HSV-1, EBV, and CMV in advanced sites of generalized Kamma JJ et al(2001)
aggressive periodontitis
Chronic • EBV-1, HSV-1, and CMV was detected
periodontitis • EBV(32%,) & CMV (71%) in GCF • Contreas A et al (1999)
• CMV can be related to an inflammatory infiltrate with a • Thomasini RL et al (2012)
predominance of CD3 (+) T cells, whereas human herpes
virus 7 can be associated with an infiltrate with
predominance of T-\CD4 (+) cells.
Disease Viruses active studies
Periodontal • Epstein Barr virus(72%), CMV(67%), and co-infection with the above two Saygan I et al(2004)
abscess viruses(56%), while the herpes viruses were not detected in healthy
periodontium or after treatment of the periodontal abscess.
• CMV has been implicated in periodontal and extraoral abscesses of HIV-
infected individuals. It is suggested that reactivation of a periodontal Eres G et al (2011)
herpes virus latent infection impairs the periodontal host defense and
permits bacterial pathogens to enter the gingiva, causing periodontal
abscess.
HIV- • CMV is the most common herpes virus in HIV-associated periodontitis. Cobb M et al(2003)
associated • EBV-1 -subgingival sites & EBV-2 was detected in 57% of biopsies from
periodontitis HIV-associated periodontitis lesions. Blackbourn DJ et
• HSV, EBV, CMV, &HSV-8 genomes in the saliva of HIV-infected al(1998)
individuals.
• HPV was detected in the GCFof HIV-positive patients under highly active
anti-retroviral treatment (HAART), independently of the periodontal
conditions
Syndromes • Cytomegalovirus was detected in periodontitis lesions in Guillain–Barre Ambili et al 2013
syndrome, Kostmann syndrome, Papillon– Lefevre syndrome, Fanconi’s
anemia, and Down syndrome.
• Natural killer cells play a crucial role in the antiherpes viral host defense.
The suppressed killer cell activity in these syndromes might have been
induced by CMV as an immunoevasive strategy.
Peri- • Significant correlation was found b/w the presence of HCMV-2 and EBV-1
implantitis genotypes and the clinical parameters of peri-implantitis.
• high prevalence of HCMV and EBV in subgingival plaque Jankovic S et al(2011)
CONCLUSION
• According to currently accepted hypothesis on the etiopathogenesis of
periodontitis, bacteria are imperative for the development of periodontitis.
However bacterial-host interaction does not suffice to explain the
localized distribution and the periods of exacerbations and quiescence
during tissue breakdown.
• It is hypothetized that an active herpes virus infection can initiate
periodontal tissue breakdown.
• Ongoing research on antiherpes virus vaccination may offer hope for
prevention of periodontitis in large group population.
• The detection of virus within periodontal pockets by various studies
proves that virus do have a role to play in periodontitis.
• The virus infection may be primary infection causing bacterial
periodontitis as a superinfection or it may be the bacterial host response
resulting in reactivation of latent virus then affecting the severity and
progression of periodontitis.
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