2. THE VIRUS
Group: Group I (dsDNA)
Order: Herpesvirales
Family: Herpesviridae
Subfamily: Alphaherpesvirinae
Genus: Simplexvirus
Species
Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)
3. The Virus
Linear double stranded DNA molecule
Enclosed in a regular icosahedral
protein coat
Lipid containing envelope covering it
TEGUMENT: between layers
4. The Infection
●
Step 1: Attachment
●
Step 2: Entry into susceptible
cells following attachment
●
Step 3: Targeting of the virion to
the site where it will reproduce
●
Step 4: Uncoating of the virion—
separation of protein coat from
nucleic acid
5. The Infection
●
Step 5: Synthesis of protein and replication ofStep 5: Synthesis of protein and replication of
nucleic acidnucleic acid
●
Step 6: Maturation of the viral particlesStep 6: Maturation of the viral particles
●
Step 7: Cell lysisStep 7: Cell lysis
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Step 8: Spreading of the virusStep 8: Spreading of the virus within the hostwithin the host
●
Step 9: Shedding of the infectious virions in salivaStep 9: Shedding of the infectious virions in saliva
●
Step 10: Transmission to the next host, therebyStep 10: Transmission to the next host, thereby
repeating the infectionrepeating the infection
6. The Dormancy
●
Some viruses spread
to axons
●
Persist in latent
stage in trigeminal ganglion
● Endogenous reactivation
● Viruses return to periphery
● Cause vesicular exanthem
7. The disease
Virus Disease Mode of
transmission
Involved sites
Herpes Simplex Virus 1 Stomatitis –CHILDREN
ADULTS: gingivostomatitis,
eczema,whitlow
keratoconjunctivitis,
esophagitis,
pharyngotonsillitis,
meningoencephalitis
Infected saliva and
oral and peri-oral
lesions
Pharynx, lips, eyes,
skin above waist
Herpes Simplex Virus 2 Herpes genitalis, neonatal
herpes
Sexual contact Genitalia, skin below
waist
8. The Features – Herpetic
gingivostomatitis
➢ Highly visible and acutely symptomatic primary infection
➢
Transmitted by droplet spreaddroplet spread or contact with lesions
➢
Age: Typically a childhood I infection seen between the
ages of 2–4 years, but increasingly seen in the mouth
and/or pharynx in older patients.
➢
Gender : M = F.
➢
Abrupt onset, with development of fever, irritability,
headache, & pain on swallowing.
➢
Incubation period: 5 -20 days
12. Histopathology : Epithelium
●
The herpetic vesicle is an intra epithelial blister filled
with fluid
●
Infected cells are swollen with pale yellow
eosinophilic cytoplasm and large nuclei
●
AKA Ballooning Degeneration
●
Acantholysis, Nuclear clearing, Nuclear Enlargement
●
Cells are KA TZANCK CELLS
16. Diagnosis – Cytologic smear
●
Puncturing an intact
vesicle and expressing
fluid on the slide
●
Stained and examined for
viral cytopathic effects
●
Non specific for HSV
Two basic types of herpes simplex infection. Lytic infections (right) commonly occur after endocytosis of herpes virus into keratinocyte. Replication and reassembly ensues that overwhelms host cell and causes it to burst, which releases large numbers of viruses. Latent infections (left) commonly occur in the cell body of neurons, where viral DNA remains
dormant within the cytoplasm or nucleus until activated to replicate and migrate along a
neural axis to an epithelial surface.
HSV 1 and 2 genomes are antigenically related and similar
HSV 2 is more neurovirulent and more resistant to antiviral drugs
PIC: only RELEASE of virus
Virus released via endoplasmic reticulum and golgi to cell surface
(b) Electron micrograph of virus particles budding from the surface of a human cell. The virion on the left has completed the process.
3 rd point before : Pathogen remains permanently after primary infection subsides
REACTIVATED BY PROLONED SUNLIGHT EXPOSURE, TRAUMA, FEVER, IMMUNOSUPPRESSION, STRESS AND ANXIETY
Pathogen return via same route
Exanthem = fever blisters
Stomatitis = primary infection
Top right – herpes stomatitis
Bottom right – labialis [ vesicles ]
Bottom left – gingivostomatitis
Numerous pinhead yellow fluid-filled pinhead vesicles –COLLAPSE → small red lesions with an erythematous halo –ENLARGE → Central areas of ulceration covered by yellow fibrin –COALESCE → larger ulcers
Recurrent infections occur at the site of inoculation or along distribution of the ganglion
COLD SORES: occurs following upper
respiratory tract infection
Recurrent herpes labialis. A, Early stages consisting of fluid-filled viral vesicles. They ulcerate and resolve as B, Late stage demonstrating brownish crusted lesions.
Intra oral Herpes: Punctate with red/ white bases that disappear
Cells absorb fluid and swell
Herpes simplex. Early and late stages of intraepithelial viral vesicle formation. A, Incipient vesicle formation early in prodromal stage before presence of a clinically visible vesicle exhibiting ballooning degeneration, nuclear margination, and multinucleation of the spinous layer of keratinocytes (viral cytopathic changes).
B, Fully developed but intact intraepithelial viral vesicle that contains fluid, virally altered keratinocytes, large numbers of viruses, and necrotic debris.
C, Photomicrograph of cytologic smear of viral vesicle contents that reveals
enlarged and ballooned keratinocytes and associated leukocytes.
SOME OTHER CELLS SHOW LIPSHCUTZ BODIES
Diagnosis : based on cf
IMMUNOSTAINS: use monoclonal abs to identify specific types and subtypes of Herpes.