Herpes Simplex viruses 1 and 2

 HUMAN HERPESVIRUSES

Ø  Infect only humans.

Ø  Herpesviridae family contains enveloped, double-stranded DNA viruses with large complex genomes.

Ø  They replicate in the nucleus of a wide range of vertebrate hosts.

·       Of the more than 100 known herpesviruses, 8 routinely

I.         STRUCTURE OF HERPESVIRUSES

Ø  The herpes viruses are large, enveloped viruses that contain double-stranded DNA.

Ø  The virion is 150 nm in diameter.

Ø  The DNA core is surrounded by an icosadeltahedral capsid containing 162 capsomeres.

Ø  This capsid is enclosed by a glycoprotein-containing envelope.

Ø  Encode several glycoproteins for viral attachment, fusion, and for escaping immune control.

Ø  As enveloped viruses, the herpesviruses are sensitive to acid, solvents, detergents, and drying.

II.         TRANSMISSION

•         HSV 1: transmitted primarily in saliva.

•         HSV 2: transmitted by sexual contact

•         Oral–genital sexual activity: HSV-1 infections of the genitals and HSV-2 lesions in the oral cavity. –10–20% of cases.

III.         REPLICATION

•         Herpesvirus replication is initiated by the interaction of viral glycoproteins with cell surface receptors.

•         Virus fuse its envelope with host plasma membrane, releasing the nucleocapsid into the cytoplasm.

•         Enzymes and transcription factors are carried into the cell in the tegument of the virion.

•         The nucleocapsid docks with the nuclear membrane and delivers the genome into the nucleus, where the genome is transcribed and replicated.

•         The viral genome is transcribed by the cellular DNA dependent ribonucleic acid (RNA) polymerase and is regulated by viral-encoded and cellular nuclear factors.

•         The virus is released by exocytosis or cell lysis.

•         Virus avoids antibody by cell-to-cell spread and syncytia.

IV.         PATHOGENESIS AND IMMUNITY

·       The mechanisms involved in the pathogenesis of HSV-1 and HSV-2 are very similar.

·       Both viruses initially infect, replicate in mucoepithelial cells, cause disease at the site of infection, and then establish latent infection of the innervating neurons.

·       HSV-1 is usually associated with infections above the waist, and HSV-2 with infections below the waist.

1          Gingivostomatitis

–Occurs primarily in children and is characterized by fever, irritability, and vesicular lesions in the mouth.

–The primary disease is more severe and lasts longer than recurrences.

–The lesions heal spontaneously in 2 to 3 weeks.

–Many children have asymptomatic primary infections.

2          Herpes labialis

–      Fever blisters or cold sores are the milder, recurrent form

–      Characterized by crops of vesicles, usually at the mucocutaneous junction of the lips or nose

–      Recurrences frequently reappear at the same site.

3          Keratoconjunctivitis

–      Characterized by corneal ulcers and lesions of the conjunctival epithelium.

–      Recurrences can lead to scarring and blindness.

4          Encephalitis

–      Necrotic lesion in one temporal lobe.

–      Fever, headache, vomiting, seizures, and altered mental status

5          Herpetic whitlow

–      Pustular lesion of the skin of the finger or hand.

–      It can occur in medical personnel as a result of contact with patient’s lesions.

6          Herpes gladiatorum

–      Wrestlers and others who have close body contact.

–      Vesicular lesions on the head, neck, and trunk.

7          Disseminated infections

–      Such as esophagitis and pneumonia,

–      Occur in immunocompromised patients with depressed T-cell function.

        HSV-2 infections

8          Genital herpes

–      Painful vesicular lesions of the male and female genitals and anal area

–      The lesions are more severe and protracted in primary disease than in recurrences.

–      Primary infections are associated with fever and inguinal adenopathy.

–      Asymptomatic infections -source of infection of other individuals

•Men: prostate or urethra

•Women: cervix

9          Neonatal herpes

–      Originates chiefly from contact with vesicular lesions within the birth canal.

–      Varies from severe disease (e.g., disseminated lesions or encephalitis) to milder local lesions (skin, eye, mouth) to asymptomatic infection.

–      Prevented by performing cesarean section on women with either active lesions or positive viral cultures.

–      Neither HSV-1 nor HSV-2 causes congenital abnormalities to any significant degree.

–      Latent infection occurs in neurons and results in no detectable damage.

V.         LABORATORY DIAGNOSIS

1. Specimens:

•       Saliva, vesicle fluids, conjunctival fluids, corneal scrapping, skin swab and CSF.

•       Depends upon the site of infection.

2. Microscopy:

•       smear preparation: Smear is prepared from the lesion and stained with 1% aqueous solution of toluidine blue for 15 seconds. Multinucleated giant cells are visualized in a positive smear.

•       Giemsa stain can also be used to see inclusion bodies.

3. Electron microscope

4. Virus Culture:

•       Primary human embryonic kidney cell line culture, Hela cell, Human amnion, Hep2

•       Cytopathic effect should be visualized within 1-3 days

5. Serology:

•       ELISA, neutralization test, Complement fixation test (CFT), Immunofluorescent test

7. Molecular diagnosis:

•       PCR, DNA probe

VI.         TREATMENT

–      Acyclovir

–      Penciclovir

–      Valacyclovir

–      Famciclovir

–      Adenosine arabinoside (ara-A)

- Trifluridine.