Explore Herpesviridae: structure, 8 human types, and detailed HSV-1 & HSV-2 pathogenesis. Understand diseases like cold sores, genital herpes, encephalitis & tr
HERPESVIRIDAE Family Overview Etymology: From Greek herpein — "to creep," reflecting the spreading nature of skin lesions. Significance: Second most common cause of human viral disease, after influenza and cold viruses. Structure (shared by all members): - Large, enveloped, double-stranded DNA viruses - Icosahedral capsid - Tegument layer between capsid and envelope - Surface glycoproteins mediating attachment and entry - DNA replication occurs in the nucleus of host cells The 8 Human Herpesviruses: 1. Herpes Simplex Virus type 1 (HSV-1) 2. Herpes Simplex Virus type 2 (HSV-2) 3. Varicella-Zoster Virus (VZV) — HHV-3 4. Epstein-Barr Virus (EBV) — HHV-4 5. Cytomegalovirus (CMV) — HHV-5 6. Human Herpesvirus 6 (HHV-6) 7. Human Herpesvirus 7 (HHV-7) 8. Human Herpesvirus 8 (HHV-8) General Characteristics (apply to ALL herpesviruses): - Most primary infections are asymptomatic - After primary infection, virus establishes lifelong latency in host tissues - All are capable of reactivation causing recurrent disease - In tissue culture: produce intracellular inclusion bodies and cytopathic effect (ballooning and rounding of cells → cell death) --- 1. HERPES SIMPLEX VIRUS (HSV) Epidemiology - Extremely widespread in the human population - Establishes latency in sensory nerve ganglia - Reactivation is common Types Feature HSV-1 HSV-2 --- --- --- Primary site Oropharynx Genitals Transmission Skin contact, inhalation, autoinoculation Sexual intercourse Latency site Trigeminal ganglion Sacral ganglia - Both types are structurally and morphologically identical - Share significant gene sequence homology with serological cross-reaction Pathogenesis 1. Virus replicates at the initial infection site (skin/mucosa) 2. Travels retrograde along neurons to sensory ganglia 3. Establishes latency — antibodies cannot prevent this 4. Reactivation triggered by: UV light, fever, hormonal changes, surgical trauma, stress, immunosuppression Diseases caused by HSV-1 1. Acute Gingivostomatitis - Most common primary HSV-1 manifestation - Occurs in early childhood - Fever + painful vesicular lesions on gums, lips, oral mucosa - Vesicles rupture → red-based ulcers → may be secondarily infected with Candida albicans (white coat) 2. Herpes Labialis (Cold Sores / Fever Blisters) - Reactivation of latent HSV-1 - Vesicles at the vermilion border of the lip - Triggered by sunlight, fever, stress 3. Herpetic Keratoconjunctivitis - Corneal ulcers and conjunctival epithelium lesions - Recurrence appears as dendritic ulcer — pathognomonic - Repeated recurrences → permanent corneal scarring → blindness 4. Herpes Encephalitis - Rare but severe - Involves the temporal lobe - High mortality; survivors have neurological sequelae - Most common cause of fatal sporadic encephalitis 5. Herpetic Whitlow - HSV infection of the fingers - Occupational hazard for healthcare workers (dentists, nurses) - From contact with infected oral/genital secretions 6. Eczema Herpeticum - Widespread HSV infection superimposed on pre-existing eczematous skin - Risk of bacterial superinfection 7. Disseminated HSV - Occurs in immunocompromised patients - Can involve multiple organs Diseases caused by HSV-2 1. Genital Herpes - Sexually transmitted - Males: vesiculoulcerative lesions on the penis - Females: lesions on cervix, vulva, vagina, perineum - Primary episode more severe than recurrences 2. Aseptic Meningitis - Self-limited - Associated with primary HSV-2 infection 3. Neonatal Herpes - Acquired in utero, during delivery, or after birth - Most commonly from HSV-2 (occasionally HSV-1) - Can be localised (skin/eyes/mouth) or disseminated (CNS, liver) - High mortality if untreated Immune Response & Evasion - Induces both humoral and cell-mediated immunity - Evasion mechanisms: - Mutation of surface membrane proteins - Blocks interferon induction - Blocks dendritic cell maturation - Inhibits complement activation Laboratory Diagnosis Specimen: Vesicular fluid, corneal scrapings 1. Tzanck Smear — from base of vesicle; Wright stain shows multinucleated giant cells with "ground glass" chromatin (Tzanck cells) 2. Direct Immunofluorescence — monoclonal antibodies conjugated with fluorescent dye; viral inclusion bodies appear as bright green intranuclear particles under UV microscope 3. Viral Isolation — tissue culture (human diploid fibroblasts, human amnion, human embryonic kidney); cytopathic effect (syncytium formation) seen in 24–48 hours 4. Serology — IgM detection; useful for primary infection diagnosis Treatment - Acyclovir (topical, oral, or IV) - Mechanism: inhibits viral DNA polymerase - Does not eliminate latency --- 2. VARICELLA-ZOSTER VIRUS (VZV) Overview - Causes two distinct diseases: - Varicella (chickenpox) — primary infection - Herpes Zoster (shingles) — reactivation --- A. Varicella (Chickenpox) Transmission: - Airborne droplets - Direct contact with vesicular fluid of chickenpox or zoster patients Pathogenesis: 1. VZV infects mucosa of upper respiratory tract 2. Multiplies in regional lymph nodes 3. Primary viremia → spreads to liver and spleen 4. Secondary viremia → spreads to skin → rash 5. Establishes lifelong latency in dorsal root ganglia Clinical Features: - Incubation: 10–21 days - Mild fever followed by characteristic rash - Rash progression: macules → papules → vesicles → crusts - Rash begins on trunk → spreads to face and limbs - Crusts shed without scarring in uncomplicated cases - Cropping is characteristic — lesions in different stages simultaneously Complications: - Pneumonia — especially dangerous in adults; can be fatal - Fulminant encephalitis — rare; may manifest as Reye's syndrome (triggered by salicylate use during infection — do not give aspirin to children with varicella ) Congenital Varicella Syndrome: - Primary maternal infection in 1st trimester → congenital varicella syndrome (serious, potentially fatal) - Features: skin lesions, limb hypoplasia, chorioretinitis, CNS defects Neonatal Varicella: - Maternal infection near time of delivery → widely disseminated neonatal infection - Mortality rate: 35% - If rash began 1 week before delivery → maternal antibodies transferred via placenta → baby is protected Immune Response: - Early stages evoke little or no adaptive immune response to VZV antigen - Later: humoral + cell-mediated immunity develops --- B. Herpes Zoster (Shingles) Definition: Reactivation of latent VZV from dorsal root ganglia Who gets it: Adults and immunocompromised patients Clinical Features: - Painful vesicular rash confined to a single dermatome (area of skin innervated by one dorsal root ganglion) - Prodrome of pain before rash appears - Unilateral distribution Complications: - Ophthalmic zoster (trigeminal nerve involvement): keratitis, conjunctivitis, iritis — risk of blindness - Bell's palsy : facial nerve involvement via cranial nerves - Post-herpetic neuralgia (PHN): - Very painful; persists for months after rash resolves - Due to nerve damage from zoster - Does NOT respond to antiviral treatment Laboratory Diagnosis (VZV) Specimen: Vesicular lesion smears 1. Tzanck Smear — multinucleated giant cells with ground glass chromatin 2. Direct Immunofluorescence — bright green intranuclear particles under UV 3. PCR — for viral DNA detection (most sensitive) 4. Serology — specific VZV antibodies using CFT, NT, or ELISA Treatment - Drug of choice: Acyclovir - Mechanism: inhibits viral DNA polymerase - Used in: immunocompromised patients, complicated chickenpox (pneumonia, keratitis), neonatal varicella - Does not eliminate latency - Post-herpetic neuralgia does not respond to antivirals Prevention Type Method --- --- Active immunization Live attenuated varicella vaccine — single dose, ages 1–12 years Passive immunization Varicella-Zoster Immunoglobulins (VZIG) VZIG given to: - Immunocompromised children exposed to VZV - Mothers infected near term (before delivery) --- 3. CYTOMEGALOVIRUS (CMV) Overview - Highly prevalent pathogen - Healthy adults: usually asymptomatic - High-