Herpesviridae: HSV-1, HSV-2 Pathogenesis & Clinical Diseases

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 → r