Herpesviridae Family

1. Herpesviridae Family

2. Introduction • Herpes Viruses are a leading cause of human viral diseases, second only to influenza and cold viruses. • Are capable of causing overt disease or remaining silent for many years only to be reactivated. • Name Herpes comes from the Latin herpes which, in turn, comes from the Greek word herpeinwhich means to creep.

3. Structure Large, enveloped DNA viruses Icosahedralcapsids DNA replicates in the nucleus of host cells

4. General Characteristics • Most infections are asymptomatic • They remain latent in the host after recovery from primary infection • All herpes viruses cause recurrent infections by reactivation of viral replication

5. General Characteristics • In tissue culture they produce: • Intracellular inclusion bodies • Cytopathic effect: balloning and rounding of infected cells followed by cell death • Some are oncogenic: HSV-2, EBV, and HHV-8 • They can cause severe disease in immuno-compromised hosts and neonates

6. Classification There are 25 families in the Herpeotoviridae but only 6 of them infect man with any regularity. • Herpes Simplex virus Type 1 (HSV-1) • Herpes Simplex virus Type 2 (HSV-2) • Epstein Barr virus (EBV) • Cytomegalovirus (CMV) • Varicella Zoster virus (VZV) • Human Herpes virus 6 • Human Herpes virus 8

8. Types of Herpes viruses

11. Herpes Simplex Viruses • Extremely wide spread in human population • Establish latency in nerve cells • Reactivation is common • There are two distinct types of HSVs: type 1 &type 2 • Structurally & morphologically indistinguishable • Exhibit sequence gene homology with serological cross-reaction • Can be distinguished by restriction enzyme analysis of viral DNA and mode of transmission

12. Epidemiology • One of the most common viral infections. • 60-90% of adults show detectable Abs. • Humans are the only natural hosts and source of infection • The virus is found in the lesions on the skin but can be present in body fluids including saliva and vaginal secretions. • Asymptomatic carriers: more important specially HSV 2.

13. Epidemiology • Transmission occurs mainly by close contact for HSV1 and HSV-2 is normally spread sexually. • An infant can be infected at birth through birth canal or transplacentally.

14. Virus enters through defects in skin or mucus membrane Multiplies locally Cell to cell spread Enters cutaneous nerve fibres Transported intra-axonally to ganglia Replication occurs Centrifugal migration To skin

15. Pathogenesis of HSV 1 &2 Sensory ganglia Replication Initial infection site Migration through Neuron reactivation Reactivation is through stress stimuli such as UV light, fever, hormonal changes, surgical trauma to the neuron latency Antibodies do not prevent reactivation HSV-1: trigeminal ganglia HSV-2: sacral ganglia

16. Diseases caused by HSV-1 1- Oropharyngeal infections: • Acute gingivostomatitis: occurs in early childhood • Fever, • painful vesicular lesions ; on gums, lips & oral mucosa, • these vesicles thin walled, umbilicated, roof of which rupture leaving a red based ulcer which heal without scarring. • Herpes labialis (fever blisters or cold sores) • Milder recurrent form • Crops of vesicles at the mucocutaneous junction of lips or nose

17. Herpes Labialis Acute herpetic Gingivo-stomatitis

18. 2- Herpetic Keratoconjunctivitis: • Corneal ulcers and lesions of conjunctival epithelium • Recurrence takes the appearance of dendritic ulcer or vesicles on the eye lids • Recurrent keratitis may lead to permanent scarring ending with blindness

19. Keratitis Vesicles around eye lid

20. 3- Encephalitis • Rare • Involves temporal lobe with high mortality 4- Herpetic Whitlow: • Fingers herpes infection • In health care workers e.g. dentists & nurses 5- Eczema Herpeticum: • Involves known eczematous areas with bacterial superinfection 6- Disseminated infection: • Fatal esophagitis or pneumonia in immuno-compromised patients

21. Herpetic Withlow Eczema Herpeticum

22. Diseases caused by HSV-2 1- Genital herpes: • Sexually transmitted • Vesiculo-ulcerative lesions of penis in males and cervix, vulva, vagina, & perineum of females 2- aseptic meningitis: Self limited 3- Neonatal Herpes: • Acquired in utero, during, or after birth • Severe in the newborn. So pregnant females with recurrent herpes should deliver by CS

23. As a general rule • HSV 1 produces ‘above the waist’ lesions and • HSV2 produces ‘below the waist’ lesions.

24. Laboratory Diagnosis • Laboratory diagnosis of herpes infection can be done by: • Microscopy • Immunofluorescence • Virus isolation • Serology • DNA detection.

25. Microscopy Specimen: Vesicular fluid, Corneal scrapping 1- Direct Virus Demonstration: a) Light Microscopy: Tzanck smear – • smear from the base of vesicles & stained with 1% aq. soln. of toluidine blue ‘O’ • shows multinucleated giant cells with faceted nuclei & homogenously stained ‘ground glass’ chromatin (Tzanck cells)

26. Giemsa stained smear – IntranuclearCowdry type A inclusion bodies • Electron microscopy • HSV & HZV cannot be differentiated by light microscopy

27. B) Direct Immunofluorescence: • Cell scrappings 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

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

29. Serology: useful in the diagnosis of primary infection, Ab (IgM) detection by ELISA, NT or CFT. • PCR: for detection of viral DNA in CSF

30. Treatment • Inhibits viral DNA polymerase enzyme • Topical, oral, or IV Acyclovir Doesn’t affect latency

31. Varicella –Zoster Virus (VZV) Causes 2 major diseases Varicella (chicken pox): primary infection usually in childhood Zoster ( shingles): reactivation of an earlier varicella

32. 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

33. 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

34. Clinical Picture • Incubation period: 10-21 days • Symptoms: mild fever & rash • Rash: first appears on the trunk, then face but sparing distal parts of limbs (Centripetal distribution) • Flat macules become papules then vesicles • Followed by crust formation • The crust is often shed off and heals without scarring

35. 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: Hemorrhagic, bullous lesions, heal with scar

37. Complications 1- pneumonia especially in adults, may be fatal 2- rarely: fulminant encephalitis, which may be a manifestation of Reye’s syndrome that occurs as a consequence of salicylates intake during infection 3- Myocarditis, nephritis, acute cerebellar ataxia, meningitis and encephalitis

38. Congenital Varicella Syndrome & Neonatal Varicella • Primary maternal infection during the 1st trimester may lead to congenital varicella syndrome ( serious & fatal): skin lesions, hypoplasia of limbs, chorioretinitis & CNS defects • 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, maternal Abs transferred via placenta – baby gets the infection but escapes clinical disease

39. 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 (dermatome)

40. Complications: • If affecting the eye via trigeminal nerve: keratitis, conjunctivitis & iritis • It can affect the brain via the cranial nerve leading to Bell’s palsy • Post Herpetic neuralgia: Very painful, Likely due to nerve damage from zoster outbreak, Lasts for months after zoster resolves

41. Laboratory Diagnosis • Specimen: Vesicular lesions smears 1- Direct Virus Demonstration: a) L/M: 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)

42. B) Direct Immunofluorescence: C) PCR: for detection of viral DNA 2- serology: Specific VZV Abs using CFT, Nt, or ELISA