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Viruses in periodontics
1.
2. CONTENTS
• Introduction
• Virus classification
• Viral components and structure
• Replication of viruses
• Host response to viral infections
• Human immunodeficiency virus
• Structure
• Pathogenesis
• Periodontal conditions
• Herpes Viruses in periodontal disease
• Structure
• Herpesviral–bacterial model of periodontitis
• Evidence for the viral etiology
• Challenges for the viral hypothesis
• Summary
• References
3. 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 – first described – filterable agents
• “Living chemicals” – crystallised like chemicals- Stanley 1935
extraction of “infectious nucleic acid” - Geirer & Schramm 1956
• Organisms at the edge of life
4. • The etiopathogenesis of periodontal disease is a complex process
• Bacterial etiology alone has not been able to substantiate…
• Recently, various HHVs have emerged as putative pathogens in
destructive periodontal disease
Slots et al. 2006
• HHV-bacterial pathogen model
Slots et al 2007
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
6. BACTERIA VIRUS
Intercellular organisms Intracellular organisn
Size Larger (1000nm) Smaller (20 - 400nm)
Living
attributes
Living organism
Opinions differ on whether viruses
are a form of life or organic
structures that interact with living
organisms.
Structures
DNA and RNA floating freely
in cytoplasm. Has cell wall
and cell membrane.
DNA or RNA enclosed inside a coat
of protein.
Ribosomes
Present Absent
Reproduction
Fission- a form of asexual
reproduction
Invades a host cell and takes over the
cell causing it to make copies of the
viral DNA/RNA. Destroys the host
cell releasing new viruses.
Treatment
Antibiotics
Vaccines prevent the spread and
antiviral medications help to slow
reproduction but can not stop it
completely.
7. 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
9. 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
10. CAPSID
• Shell made of protein building blocks or promoters
• Self assemble into larger capsomere – then into virion capsid
• Simplest structures - symmetrical
i. Helical – form rods
ii. Icosahedral – approximation of a sphere
11. ENVELOPE
• Similar to cellular membranes
• Consists of lipids , proteins and glycoproteins
• Glycoproteins – extend from surface , act as virus attachment
proteins (VAP) , are major antigens for protective immunity
14. 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
15. 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
17. III] NON SPECIFIC FACTORS
1. Fever
2. Interferon Production
3. Natural Killer Cell Activity
18. 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
20. 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
21. IF
N
Degrade
viral RNA
Cytotoxic
T cell
activity
Expressio
n of
adhesion
proteins
Productio
n of
cytotoxic
factorsMitogenes
is of B
cells
APC
function
Effects on
macropha
ge
NK cell
activity
1. synthesis of lysosomal enzymes
2. Expression of receptors for Fc
portion of Ig
3. Decreased migration of
macrophages – expression of MIF
4. Production of IL 1 , TNF alpha
– augment lymphocyte activation
5.Contribute to T cell response -
enhance APC function of activated
macrophagess
22. 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
25. 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
28. 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
function
•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.
•So chemotaxis, antigen presentation and
intracellular killing is diminshed.
•Activity of NK cells and cytotoxic T cells is affected
MONOCYTE –
MACROPHAGE FUNCTION
HUMORAL
MECHANISM
29. LINEAR GINGIVAL ERYTHEMA
• A persistent , linear , easily bleeding, erythematous gingivitis
• Possible etiology – candida dubliniensis
• Prevalence in HIV patients – 0-49%
30. 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%
31. HIV latently infecteted cells
Activation of membrane receptors by
pathogens and cytokines
Turns on down stream signaling
pathways
Activation of transcription factors like
NF-kB
Activation of
proinflammatory genes
Production of
proinflammatory cytokine
HIV LTR
transactivation
Production of new
virions
Co infection
PROPOSED MODEL OF HIV REACTIVATION DURING
CO-INFECTION
34. VIRUS REPLICATION
Capsid Nonstructural proteins
DNA
Attachment and
penetration by fusion
Nucleus DNA
genome
mRNA
DNA
Protein
Immediate early
Protein synthesis
LATENT
Early
Protein synthesis
and genome replication
ACTIVE
Late
Protein synthesis
(structural protein)
Exocytosis and release
Assembly and release
Lysis and release
35. 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
36. 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.
37. Replication in epithelial cells
Viral nucleocapsids ascend local
sensory neurons by reterograde
axonal transport
Establish lifelong latency in
corresponding spinal or cerebral
ganglion
Reactivation occurs at any time
Virus replication in infected neurons
Virus transproted down the axon to
original position
38. • 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).
39. 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.
40. 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
41. 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.
42. 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
43. 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.
44. 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.
45. HERPESVIRAL–BACTERIAL MODEL OF PERIODONTITIS
Healthy gingiva
Bacterial biolfilm
Gingivitis
Herpes viruses activation
Periodontopathic properties
1. Inflammation
2. Collagen degradation
3. Bone resorption
Sufficient time span
Destructive periodontal disease
•Macrophages with
latent HSV & HCMV
•B cells with latent EBV
•T cells with latent
HSV & CMV
1. Immunosuppression
from infection or
cytotoxic therapy
2. Inflammation
3. Psychosocial or
nutritional stress
4. Hormonal changes/
pregnancy
5. Physical or chemical
tissue injury
6. Tobacco usage
7. Aging
8. Others
Cytokines or Enzymes
1. IL-1β
2. TNF-α
3. PGE2
4. MMPs
Immunosuppression &
upgrowth of pathogenic
bacteria
1.P .gingivalis
2. T. forsythia
3.A. actinomycetemcomitans
4. D. pneumosintes
Cytotoxicity/Tissue necrosis
with severe
immunosuppression
1. HIV-infection
2. Nutritionally stressed
children/adolescents
46. 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
47. 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.
48. 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
49. 4. Higher frequency of virus detection in subgingival plaque from
periodontaly diseased than from healthy sites
• Saygun et al 2002...
• Frequency of detection lower compared to previous studies
VIRUS CHRONIC
PERIODONTITIS
HEALTHY
HCMV DNA 44 % 14.3%
EBV DNA 17 % 14.3%
HSV DNA 6.7% -
50. 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
51. 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
52. • 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
53. 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
54. 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
55. 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
56. 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.
58. • Contemporary Oral Microbiology and Immunology- Slots,
Taubman.
• Textbook of Microbiology 7th Edition Ananthnarayan and Paniker
• Pushpa S P, Soumya B G .Herpesviruses in Human Periodontal
disease.Reality or Myth…? J. Int Oral Health 2010,2(2)59-64
• Jorgen slots Herpes viruses in periodontal Disease Perio 2000, Vol.
38, 2005, 33–62
• I Cappuyns, P Gugerli, A Mombelli . Viruses in periodontal disease
– a review Oral Diseases 2005, 11, 219–229
• Jorgen slots. Human viruses in periodontitis Perio 2000, Vol. 53,
2010, 89–110
• Uppoor and Nayak HIV and Periodontal Disease: Redemption or
Resurrection, J AIDS Clinic Res 2012,
Editor's Notes
Becoz their small size allowed them to pass through filers used to retain bacteria
Latin virus = poison or toxin
–since they possess genes and evolve by natural selesction and reproduce by creating multiple copies of themselves. But they donot have a cellular structure
Which supports the role of viruses in periodontal etiopathogenesis
`Regressive Theory - It proposes that viruses arise from free-living organisms like bacteria that have progressively lost genetic information to the point where they become intracellular parasites dependent upon a host to supply the functions they have lost.
Run-away RNA - It proposes that viruses arise from the host-cell RNA or DNA, which gain a self-replicative but parasitic existence. One or a few genes (or the mRNA) acquires the ability to replicate and evolve independently of its host gene.
Coevolution - This theory proposes that viruses originated and evolved along with the most primitive molecules that first contained self-replicating abilities. While some of these molecules were eventually collected into units of organization and duplication termed cells, other molecules were packaged into virus particles that coevolved with cells and parasitized them.
they live in-between cells ,,,they infiltrate the host cell and live inside the cell)
Virus naes may describe their characteristics, diseade associates , or eve where they were first identified
Acronym for members of its family
David baltimore in 19 71 classified viruses into 7 classes based on viral genome
Group VII: Double-stranded DNA viruses that replicate through a single-stranded RNA intermediate
+ss RNA – similar to m RNA
- Ss RNA – template for production of RNA
Viruses are supermolecular complexes consisting of
Peplomers – protein subunits seen as projecting spikes on ythe envelope
Capsomere – the polypeptide chemical units which are arranged symmetrically to form an impenetrable shell around nucleic acid
Protein subunits join togethr to form a polpeptide unit that is the capsomere.
Each unit is made up of 5 identical capsomeres
Each capsid is made of identical units
That form 12 adjacent vertices of the structure
Has a membrane structure which is
VAP – bind to structres on target cells
The cells act as factory providing subsrates , energy & machinery for replicati of viral genome n proteins
step in infection is recogn and attachment to target cell
VAP –specific capsomeric structures present at vertices of naked capsid , Gp of enveloped . Bind to receptors on cells
3. Penetration – infection cannot proceed until the virus penetrates the plasma membrane . Binding of virus to appropriate receptors can trigger the cell to internalise the virus by proesses the cell normally uses to uptake receptor bound molecules
Non nenveloped – enter by receptor mediated endocytosis – viropexis
Enveloped – internalised by endocytosis or their envelope can fuse with plasma memb to drive the nucleocapsid into the cytoplasm
4. uncoating- once internalised , nucleocapsid must be delivered to the site of replication and the capsid & envelope sholud be removed
5. Transcription – most imp step . Generation of mRna for protien synthesis must occur for infection to proceed. Depends on the viral genome
7. Replicaton of genome – all the viruses must have the means for synthesising MRNA n generating a genetic template for replication of genome n more mRNA
DNA virus – use cell machinery for trannscription & mrna resides in the nucleus
RNA – encode the necessary enzymes for transcription n translation
6. Protin synthesis – all viruses use host cell ribossomes , trna , machinery for posttranslational modification. Eg – viral Gp are synthesized on membrane bound ribosomes through endoplasmic reticulum and golgi apparatus and expressed in plasma memb of cell
8. Assembly – virion is built from small easily manufactured parts that enclose genome into functional package
Nucleocapsids may be assembled as empty structures to be filled with genome or assembled around the genome
Enveloped viruses – acquire membrane on association of nucleocapsid with regions of cell modifoed with viral GP
9 , relased either by cell lysis – naked capsid virues or by budding from plasma memb – enveloped viruses
10 spread of virus – i) relase of virus into EC matrix , cell – cell fusion
ii) vertical transmission of genome to daughter cells
Principal Component
Critical in eliminating infected cells
T cells – eliminate primary infection
i) lyse virus infected cells
ii) secrete lymphokines that activate macrophages
iii) secrete IFN γ
NK cells – natural cell mediated cytotoxixity
i) lyse virus infected cells
ii) contribution after activation by IFN γ
Increased temperature decreases virus replication and also destabilize certain viruses
Normal ionic environment inside the cells may be altered with increased intracellular NA concentration
Infectious particles spread through EC fluid among cells
the immune system encounters viral antigen only when cell lysis releases the virions
induce virus-specific antigens on the cell surface before cell death occurs and sometimes before viral multiplication is complete
common among enveloped virus-specific antigens are present on the cell surface and the cells release the infectious virions by budding for a short period before cell death.
Following infection Viruses persist intracellularly for extended periods
Chronic - progeny virions are released continuously, with little adverse effect on cellular metabolism. These cells express virus-specific antigens on their surface and produce abundant virus progeny, but are not killed by the infectious process. In some steady-state infections the progeny virus is released by budding through the cell membrane, and virus can spread from cell to cell without being exposed to the extracellular
Latent – Latent infections result when an infecting virus is maintained within a cell for a long time (sometimes years) without giving rise to progeny virus or damaging the cell. Cells infected in this way may express virus-specific antigens on their cell surface. Months to years after infection, the virus in these cells can be reactivated, replicate, and cause disease. The mechanisms by which viruses are maintained intracellularly for long periods and then reactivated are only incompletely understood. Many latent infections occur in sequestered areas of the body (such as the nervous system), where recognition of infected cells by the immune system is believed to be difficult. In addition, any cell that harbors a virus but does not express viral antigens is not recognized by the immune system
Integrated infection - in which all or part of the viral nucleic acid becomes integrated into the genome of the host cell. Progeny virions may never be assembled or released from the host cell. New virus-specific antigens, however, can be detected within the cell or on the cell surface
Of interference with viral infection. Induce a state if antiviral resistance in uninfected cell
Alpha – stimulated by nonspecific mechanisms
- Inhibit viral protein synthesis
That promote intracellular adhesion
Il 1 – causes T cell to produce IL2 - B cell proliferation – Ab production
IL 2 – T cell proliferation
Increased binding of NK cells
Inc metabolic activity of nk cell by production of cytolytic molecules
Coming to viruses which have a role in PD infection the HIV and herpes
1 – common type
2 similar disease in west africa. Long incubation period
Was reported as a sudden outbreak of 2 rare disease kaposis sarcoma & pnuemocystis carinii in homosexual males
Decided on the generic name
Spherical , enveloped
90-120 nm
Icosahedral – outer shell , coneshaped core – inner shell which enclose RNA
Diploid RNA with identical SS positive sense RNA copies
With viral RNA there is reverse transcriptase enzyme – characteristic to retrovirus
Integrase enzyme – integrates viral genome with host DNA
Acquires a lipoprotein envelope consisting of lipid derived from host celland GP are virus encoded
GP 120 – presents as projecting knoblike spikes on the surface – binds to CD4 receptors
GP41 – anchoring transmemb pedicles – bring abt cell fusion
3 structural genes –
gag – group specigic AG genes – has precursor protein p55 of which
P17 – matrix , p24 – major core Ag detected in serum during early stgaes before AB appears , P7 & 6 –The nucleocapsid associates with the genomic RNA (one molecule per hexamer) and protects the RNA from digestion by nucleases
Pol – codes for enzymes – p10 – proteases is required to cleave the precursor Gag polyprotein to produce structural proteins ,p51 – RT , p32 – integrase
Env – gp120 , gp 41
Nonstructural n regulatory genes
Tat ( trans activating gene ) – expression of all viral genes
Rev ( regulatir of virus gene– exp of structural genes
Nef ( negative factor gene - downregulates viral replication
Vif ( viral infectivity factor gene) – influence infectivity
Vpu ( viral protein U) – only in HIV 1 , Vpx ( HIV2) – enhance maturation n release of progeny virus.ditinguish betn hiv 1 & 2
Vpr ( viral protien R) stimulate promoter region of virus
LTR- (long terminal repeat ) – one at either end contains sequences giving promoter, enhaancer n integratio n signals
Ag and infects cells bearing CD4 Ag on the surface.
molecules required for cell fusion and virus entry.
1HIV-1 interacts with a cell-surface receptor, primarily CD4, and through conformational changes becomes more closely associated with the cell through interactions with other cell-surface molecules, such as the chemokine receptors CXCR4 and CCR5.
2. The CD4-binding site on HIV-1 gp120 interacts with the CD4 molecule on the cell surface
3Conformational changes in both the viral envelope and the CD4 receptor permit the binding of gp120 to another cell-surface receptor, such as CCR5.
4. his second attachment brings the viral envelope closer to the cell surface, allowing interaction between gp41 on the viral envelope and a fusion domain on the cell surface. HIV then fuses with the cell.
5. Subsequently, the viral nucleoid enters into the cell
Primary pathogenic mechanism
thus damping the cell mediated immune response
POLYCLONAL ACTIVATION OF bCELL
Variation is due to of heterogenesity of population studies , misdiagnosed as gingivitis
These my be different stages of same disease
That CD count is below 200 cell/ul
Immune and oral epithelial cells latently infected with HIV in gingival tissues may be an important source for HIV reactivation during chronic inflammatory events triggered by oral pathogens [3]. Evidence suggests that cytokines such as interleukin-1 [IL-1] and tumour necrosis factor-α [TNF-α] activate nuclear factor kappa B [NFκB], the principal transcription factor which can induce viral gene expression through interaction with the long terminal repeat [LTR] of the HIV provirus [4]. Interferon-γ [IFN-γ], interleukin-6 [IL-6] and TNF-α up-regulate IFN regulatory factor-1 [IRF-1] which leads to cell activation and drives HIV-1 replication [5]. Inflammatory mediator prostaglandin E2 also seems to be able to increase viral replication in T cells. IL-2 and IL-7 have also found to upregulate HIV activation in T cells [6]. Studies have shown that levels of all these inflammatory mediators are elevated in periodontitis suggesting a probable role of periodontitis in reactivation of latent HIV (Figure.1).
1) a core containing a large ds DNA genome encased within
2) an isosapentahedral capsid containing 162 capsomeres
3) an amorphous proteinaceous tegument and surrounding the capsid and tegument.
4) A lipid bilayer envelope derived from host cell memb
Envelope contains viral induced glycoproteins- which are ligands. For cellular attachment
Based on tissue tropism, pathogenesity
A – nerotropic, rapid replication cycle
B – fibroblast specific , slow
G – t or B cell specific , slow
1Virion initiates infection by fusion of the viral envelope with plasma membrane following attachment to the cell surface.
2.Capsid is transported to the nuclear pore where viral DNA is released into the nucleus.
Viral transcription and translation occur in three phases:.
Immediate early genes, which encode regulatory proteins; - shut off cell protein synthesis.
Early genes, which encode enzymes for replicating viral DNA; facilitate viral DNA replication.
Late gene encode structural proteins of the capsid of the virion. that form empty capsids.
Viral DNA is packaged into preformed capsids in the nucleus.
Virions are transported via endoplasmic reticulum and released by exocytosis or cell lysis.
1on fibroblasts, keratinocytes, endothelia cells, PMNs ,lymphocytes- may hamper tissue turnover & repair
2 , thereby predisposing to microbial superinfection
3 of periodontopathic bacteria
4and cytokine responses
5 abd hence the cytotoxic T cells cannot detect the viruses
transmission-close person –person contact by mucosal secretions or lesions.
Signals advanced stage of immunosuppresion namely in HIV infection.
than in immunocompetent persons.
Healty gingiva is affected by the bacterial biofilm
Proposed by slots in 2005
Gingivitis – influx of inflammatory cells containing latent herpesvirus
After reaching a critical viral load cytokines , enzyes storm of
Immune impairment results in ypgrowth of pathogenic bacteria
Thus herpes rely on OD bact to cause periodontitis
& pd bacteria depend on virus for initiation n progressio n of PDitis
It remained unclear if HCMV reactivation was related to the initiation or the progression of destructive periodontal disease
Could set the stage for overgrowth
, with increased PPD ,BOP, higher volumes of GCF can be collected, and samples may contain blood cells more easily.
, independent of a specific association with the local disease process
Here again, the association of two concurrent phenomena is not a proof of a cause and effect relationship.
recognising a pathophysiologyic relationship between mammalian viruses and PD disease has the potential to extend our insight into mechanism pD tissue braekdoen.
Based on the current information it seems reasonable to add PD disease to list of infectious disease that have HCMV , EBV and other viruses as contributory causes
