Herpesviridae

HSV 1,2 and VZV

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Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans The family name is derived from the Greek word herpein ("to creep"), referring to the latent, re-occurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections.
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Herpes Viruses DNA group

Most important Human Pathogens Wide Host cell range Life Long Infection Periodic reactivation Immunocompromised Large number of genes, Some viruses susceptible to Dr.T.V.Rao MD treatment.

CLASSIFICATION
(Human pathogens)
Alphaherpesvirinae
Herpes simplex virus type 1 Herpes simplex virus type 2 Varicella-zoster virus HSV-1 HSV-2 VZV CMV HHV-6 HHV-7 EBV

Betaherpesvirinae
cytomegalovirus Human herpesvirus type 6 Human herpesvirus type 7

Gammaherpesvirinae
Epstein-Barr virus MD Dr.T.V.Rao
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Infecting Humans.
Herpes Simplex virus 1 and 2 Varicella Zoster Viruses Cytomegalovirus virus Epstein Barr virus Human Herpes viruses 6, 7. Kaposi's Sarcoma associated Viruses
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Properties of Herpes Viruses.

Spherical in Shape Icosahedral 150 to 200 nm in size Genome Double stranded DNA Linear Envelope contains Glycoprotein's
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Out Standing Characteristics

Encode many enzymes. Cause Latent Infections. Indefinite persistence. Relation in Immunocompromised. Relation to Cancers.
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Herpes Virus Replication

Replicates in Host Cell Nucleus Form Cow dry A Type inclusion bodies. More than 50 different types proteins in infected cell. Large number of enzymes in DNA synthesis
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Herpes Simplex 1 and 2

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Herpesviridae
Group:Group I Family:Herpesviridae Subfamily:Alphaherpe svirinae Genus:Simplexvirus Species Herpes simplex virus 1 (HWJ-1) Herpes simplex virus 2 (HWJ-2)
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Herpes Simplex Virus

HSV are spherical in shape Ds DNA 35 proteins
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Human Herpes Virus 1 and 2

They are also called Human Herpes Virus 1 and 2 (HHV-1 and HHV-2) and are neurotropic and neuroinvasive viruses; they enter and hide in the human nervous system, accounting for their durability in the human body. HSV-1 is commonly associated with herpes outbreaks of the face known as cold sores or fever blisters, whereas HSV-2 is more often associated with genital herpes.
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Pathogenesis of HSV 1 &2

replication
Initial infection site

Sensory ganglia Migration through Neuron

Reactivation is through stress stimuli such as UV light, fever, hormonal changes, surgical trauma to the neuron

Antibodies do not prevent reactivation

latency

HSV-1: trigeminal ganglia Dr.T.V.Rao MD 13 HSV-2: sacral ganglia

Infections in Humans.( Herpes Simplex 1 and 2 )

Wide spread in Humans Broad Host Ranges. Replicate in Many types of Cells. Produce cytolytic effects

Most Common Diseases. Gingival stomatitis, Kerato conjunctivitis Encephalitis Genital diseases, New Born Infections, Latent Infections in Nerve Cells, Recurrence.
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HERPES SIMPLEX VIRUS (HSV)

HSV 1 infect the upper part of the body - mouth and the face HSV 2 infect the lower part of the body - genital infections There is little cross protection Therefore, one Dr.T.V.Rao get both the can MD infections

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Properties of Herpes Simplex Viruses Type 1 and 2

Similar in Organization Restriction Enzyme Differentiates H S V 1 contact with Saliva. H S V 2 Sexual Maternal infection ( Genital Infection spreads to New Born ) Replicates in 8-16 hours.
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Out characters of Herpes group of viruses

Out standing characters 1 Encode many enzymes Latent infections are common Persist indefinitely in infected hosts. Frequent reactivation in infected hosts Some care cancer causing.
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 About 75% of the adults show +ve for HSV 1 infection HSV 1 infections include -i. Oropharyngeal

. Children - very painful . due to kissing of elders . acute gingivostomatitis . problem of feeding

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Virus Grows in the following.

Primary and Continues Cell lines. Monkey and Rabbit Kidney, Human Amnion Syncytial formation and Giant cell formations Multiplies in Chorio Allontoic membrane Monoclonal Antibodies differentiates Type 1 and 2 types.
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Sources of infection
- Saliva - Skin lesions
Oropharyngeal lesions - Carriers

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Transmission
Close contact Skin and epithelial contact, Defects in Mucosal membrane Multiples Locally, Enters through cutaneous nerve fibers Intraaxonally to Ganglion Centrifugal Migration Recurrent manifestation in Skin and Mucosa.

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Pathogenesis.
Most Common Human Viral Infection Causes cytolytic effect causes the necrosis of cells. Infects Skin and Mucous membrane Cowdry type A inclusions are produced Multinucleated Giant cells are demonstrated
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Pathogenesis
Entry by skin or mucous membranes viral multiplication sensory nerve

lysis of cells
vesicles ulcers

root ganglia
latency
COLD FEVER SURGERY UNKNOWN
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REACTIVATION
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Predisposition of Latent Infection in

Ganglion Trigeminal HSV 1 Sacral HSV 2 Immunity. Cell Mediated ( CMI ) Predisposing Factors Axonal Injury Physical and Emotional stress U V light 80% Adults harbour Antibodies to HSV

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Clinical Manifestations
Oropharyngeal Disease Buccal Gingival Mucosa Incubation 3 to 5 days May last for 2-3 weeks Gingvo stomatitis Sub mandibular lymphadenopathy Present with painful ulcers.

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Recurrent Blisters in Herpes simplex 1

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Herpes lesions in the oral cavity

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Eye Infections and Genital Infections.

Corneal ulcerations pacifications Blindness Vesiculo ulcerative Lesions penis, Cervix, Vulva and Vagina. Manifest with Painful lesions.
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Herpes simplex 1 infecting eye

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Herpes 2 producing Genital Lesions

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Skin Infections
Infect abrasions Dentists, ( Herpetic Whitlow) Health care workers, Eczema , Burns
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Neonatal Herpes.
In Uterus At Birth After Birth. Delivery By Caesarean Section Reduces the Infection
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Neonatal Infection Normal delivery

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Other Manifestations.
Meningitis, Encephalitis Multi organ Involvement Increased incidence in Immune compromised AIDS, Haematological Malignancies.
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Recurrent infections in HSV 1 and 2

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Immunity
Mothers Ig G protects for 6 months. Primarily Ig M Later Ig g produced. Main Participants in Immunity. C M I and Killer Cells and Interferon play major role in immunity
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Laboratory Diagnosis Microscopy, Antigen Detection DNA detection PCR. Viral Isolation. Serology
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Laboratory Diagnosis
Specimen: Vesicular fluid- Corneal scrapping 1- Direct Virus Demonstration: a) L/M:
1. Tzanck smear from the base of vesicles, 1% aq. soln. of toluidine blue O shows multinucleated giant cells with faceted nuclei & homogenously stained ground glass chromatin (Tzanck cells)

2. Giemsa stained smear intranuclear Cowdry type A inclusion bodies

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 B) Direct Immunofluorescence: Cell scrapings from lesions are stained with monoclonal antibodies conjugated with a fluorescence dye. Viral inclusion bodies appear in UV microscope as a bright green Intranuclear particles

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 2- Viral Isolation: tissue culture: human

diploid fibroblasts, human amnion, human embryonic kidney: CPC (syncytium formation) seen in 24-48 hrs.

3) Serology: useful in the diagnosis of

primary infection, Ab (IgM) detection by ELISA, NT or CFT.

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Laboratory diagnosis
Childhood infections common Second peak at onset of sexual activity Viral shedding
persons with recurrences infected but asymptomatic persons
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 Useful
genital & eye infections HVZ & HSV in immunocompromised patients herpes encephalitis

Specimens
aspirate from vesicle scraping from base of ulcer serum / CSF for antibody
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Microscopy,
Tzanck Smear Intranuclear Type A Inclusion Bodies Electron Microscopy Fluorescent Antibody

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Specimens for Diagnosis.

Saliva. CSF Vesicle fluid.

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Viral Isolation in
Chick embryo In Tissue Cultures Primary Embryonic Kidney Human Amnion

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Serology,
ELISA Test Neutralization Tests Complement Fixation Tests
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Chemotherapy
Idoxuridine used topically in eye and skin infections first successful antiviral agent. Acyclovir and vidarabine helps in systemic infections Other Drugs Valaciclovir, Famiciclovir, Orally effective Foscarnet.
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Epidemiology.
World Wide Distribution HSV 1 early in life 6 months to 3 years. 70% to 90% Adults have Antibodies Poor Living Conditions HSV 2 Sexually transmitted. Risk to mother and fetus Abortions < 20 weeks gestation HSV 2 increases predisposition to HIV infection

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Varicella Zoster

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History of Chickenpox
The name chicken pox because the blisters that appeared seemed like the skin that has been pecked by the chicken..

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Herpes Virus

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Properties of Virus. Like Herpes Virus Icosahedrons shape ds DNA

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Varicella Zoster
DNA Virus

( Herpes Virus)

Varicella -Chicken pox. Contagious Disease Mainly Children Generalized Vesicular eruptions on Skin and Mucous membranes Severe manifestations in Adults and Immune compromised. Dr.T.V.Rao MD

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HERPES VARICELLA ZOSTER HVZ

Causes chicken pox -fever + characteristic rash variable incubation period 14-21 days usually mild in children and more severe in adults complications secondary infection - uncommon varicella pneumonia secondary bacterial pneumonia S aureus &
pneumococci post-infetious encephalitis generalised varicella (in immunocompromised patients) congenital and neonatal varicella
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Varicella (Chicken Pox)

Mild, highly contagious disease chiefly affecting children Mode of transmission: - airborne droplets and direct contact from varicella patients - Vesicular fluid of Zoster patients can be the source of Varicella in susceptible children

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Shingles (Herpes Zoster )

Rash Limited to Distribution of Single Sensory Ganglion In Adults and immune compromised Sporadic

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Varicella Zoster Virus (VZV)

Causes 2 major diseases Varicella (chicken pox): primary infection usually in childhood Zoster ( shingles): reactivation of an earlier varicella
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HERPES VARICELLA ZOSTER HVZ

Causes chicken pox -fever + characteristic rash variable incubation period 14-21 days usually mild in children and more severe in adults complications secondary infection - uncommon varicella pneumonia secondary bacterial pneumonia S aureus &
pneumococci post-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella
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Herpes Zoster
Primary Contact Chicken Pox Reactivation - Zoster (Partially Immune )
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Culturing virus
Grows in Human embryonic Tissue Produce inclusion bodies No difference in virus In Chicken pox and zoster infection
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Pathogenesis and Pathology

Varicella virus enter through URT/Conjunctiva. Lymph nodes Viremia Liver and spleen Secondary viremia Infects Mononuclear Cells Rash Vesicle formation
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Pathogenesis: VZV infects the mucosa of the upper respiratory tract Multiplies in the regional LNs Primary viremia and spread to liver and spleen Secondary viremia follows with viral spread to the skin Typical rash occurs

VZV remains latent in the dorsal root ganglia for life

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 Incubation period: 10-21 days Symptoms: mild fever & rash Rash: first appears on the trunk, then face and limbs Flat macules become papules then vesicles Followed by crust formation The crust is often shed off and heals without scarring Cropping is a characteristic feature of varicella rash: fresh vesicles appear in crops, so that all stages of macules, papules, vesicles & crusts are seen at the same time More severe in adults
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Clinical Picture:

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Herpes Zoster
Skin Lesions Inflammation of Sensory Nerves and Ganglia Single Ganglion Dorsal root Ganglion
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Entry of Varicella Zoster virus

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Skin lesions showing different stages

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Clinical Findings.
Varicella, Incubation 10-20 days Fever, Malaise Rash Trunk Face Limbs Buccal and Pharyngeal mucosa Lesions at all stages Macules, Papules, Vesicles, Crusts, May last 5 days, Hundreds of eruptions.
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Skin lesions of chickenpox

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Chicken pox lesions in the buccal cavity

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Herpes Zoster involving a Nerve segment

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Complications
1- pneumonia especially in adults, may be fatal 2- rarely: fulminant encephalitis, which may be a manifestation of Reyes syndrome that occurs as a consequence of salicylates intake during infection
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Congenital Varicella Syndrome & Neonatal Varicella

Primary maternal infection during the 1st trimester may lead to congenital varicella syndrome ( serious & fatal): skin

Primary maternal infection near the time of birth can lead to widely disseminated infection in the new born with mortality rate of 35%
If rash began a week or more before delivery,

lesions, hypoplasia of limbs, chorioretinitis & CNS defects

maternal Abs transferred via placenta baby gets the infection but escapes clinical disease
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Immune compromised
HIV / AIDS Malignancies. Organ transplantations Corticosteroid usage

Leukaemia's.
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HERPES VARICELLA ZOSTER HVZ

Causes chicken pox -fever + characteristic rash variable incubation period 14-21 days usually mild in children and more severe in adults complications secondary infection - uncommon varicella pneumonia secondary bacterial pneumonia S aureus &
pneumococci post-infectious encephalitis generalized varicella (in immunocompromised patients) congenital and neonatal varicella
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Pain and hyperaesthesia

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Pain and hyperaesthesia

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Pain and hyperaesthesia

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HERPES ZOSTER
Reactivation of HVZ dermatomal distribution may recur can disseminate in immunocompromised patients complications
post herpetic pain ophthalmic zoster -corneal scarring and loss of vision

DIAGNOSIS CLINICAL EM of vesicle fluid SEROLOGY Dr.T.V.Rao MD IgM detection

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Zoster.
Associated with Immune compromised. Manifest with severe pain Vesicles on trunk , head, neck Trigeminal Neuralgia
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Zoster (shingles)
Sporadic disease in adults or immunocompromised patients Results from reactivation of latent VZV Rash similar to varicella but limited to a nerve distribution to the skin innervated by a dorsal root ganglion (dermatom)
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Pain and hyperaesthesia

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Other Complications.

Encephalitis, Mother to Child transmission Varicella Pneumonia. Fatal Complications.

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Laboratory Diagnosis.
Smears --Scrapings from Lesions Demonstration of Multi nucleated giant cells Tzanck smears
DNA Demonstration Cell cultures, Fluorescent antibody ELISA PCR
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Epidemiology
Communicable Disease World wide prevalence Common in < 10 year olds. Zoster in Adults Droplet spread

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Treatment
Specific treatment is indicated mainly in Immunodeficient and elderly subjects and also in complicated with Varicella pneumonia,encephalitis,and disseminated zoster Acyclovir and Famiciclovir.

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Prevention of Chickenpox
Do nothing

Susceptible population children adults living in close proximity

Immunize live attenuated vaccine

Protect if contact with patient with chickenpox and at risk of severe disease Zoster Immune Globulin (ZIG) Dr.T.V.Rao MD 95

Vaccine available
A live modified Varicella virus lyophilised vaccine which can be stored at low temp is available for protection Children 1 -12 years given single dose. >12 years 2 doses 2 -6 weeks apart High titre serum from convalescing from herpes zoster protect Immunocompromised children. But not useful for treatment
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