Explore Herpesviridae, including HSV-1, HSV-2, and VZV. Understand pathogenesis, latency, specific diseases like cold sores, genital herpes, chickenpox, di
HERPESVIRIDAE --- OVERVIEW Definition: Large, enveloped, double-stranded DNA viruses with icosahedral capsids. DNA replicates in the host cell nucleus. Name origin: From Greek herpein = "to creep" → reflects spreading nature of skin lesions. Significance: Second leading cause of human viral disease after influenza/cold viruses. 8 Human Pathogens: HSV-1 and HSV-2 Varicella-Zoster Virus (VZV) Cytomegalovirus (CMV) Epstein-Barr Virus (EBV) HHV-6, HHV-7, HHV-8 General Characteristics (All Herpesviruses): Most primary infections are asymptomatic Establish latency after primary infection — never fully cleared All capable of reactivation causing recurrent disease In tissue culture: produce intranuclear inclusion bodies + cytopathic effect (ballooning, rounding → cell death) --- HERPES SIMPLEX VIRUS (HSV)### Types Feature HSV-1 HSV-2 --- --- --- Primary site Oral/facial Genital Transmission Skin contact, inhalation, autoinoculation Sexual intercourse Latency site Trigeminal ganglion Sacral ganglia Structurally identical; serological cross-reaction exists; share gene sequence homology. Pathogenesis- Replication at initial infection site Virus migrates via neurons → sensory ganglia → latency Reactivation triggered by: UV light, fever, stress, hormonal changes, surgical trauma Antibodies do not prevent reactivation --- HSV-1 Diseases 1. Oropharyngeal Infections Acute gingivostomatitis (children): fever + painful vesicles on gums, lips, oral mucosa → rupture → red-based ulcers → may get secondary candida infection (white coat) Herpes labialis : cold sores / fever blisters (reactivation) 2. Herpetic Keratoconjunctivitis Corneal ulcers + conjunctival lesions Recurrence → dendritic ulcer pattern Repeated recurrence → corneal scarring → blindness 3. Encephalitis Rare but high mortality Involves the temporal lobe 4. Herpetic Whitlow Herpes infection of the fingers Occupational risk: dentists, nurses 5. Eczema Herpeticum Herpes spreading into pre-existing eczematous skin Risk of bacterial superinfection 6. Disseminated Infection In immunocompromised patients --- HSV-2 Diseases 1. Genital Herpes Vesiculoulcerative lesions: penis (males); cervix, vulva, vagina, perineum (females) 2. Aseptic Meningitis Self-limited 3. Neonatal Herpes Acquired in utero, during, or after delivery Serious — can disseminate to CNS and organs --- Immune Evasion (HSV)- Mutation of membrane proteins Blocks interferon induction Blocks dendritic cell maturation Blocks complement activation --- Lab Diagnosis (HSV) Specimen: Vesicular fluid, corneal scrapings Method Finding --- --- Tzanck smear (toluidine blue) Multinucleated giant cells, "ground glass" chromatin (Tzanck cells) Direct Immunofluorescence Bright green intranuclear particles under UV Viral isolation (tissue culture) Human diploid fibroblasts / amnion / embryonic kidney → syncytium CPE in 24–48 hrs Serology IgM = primary infection --- Treatment (HSV)- Acyclovir — inhibits viral DNA polymerase Routes: topical, oral, IV Does not eliminate latency --- VARICELLA-ZOSTER VIRUS (VZV)### Varicella (Chickenpox) Epidemiology: Mild, highly contagious; mainly children Transmission: Airborne droplets Direct contact with varicella patients Vesicular fluid of zoster patients (source for susceptible children) Pathogenesis: Infects upper respiratory mucosa Multiplies in regional lymph nodes Primary viremia → liver and spleen Secondary viremia → skin → rash Remains latent in dorsal root ganglia for life Clinical Picture: Incubation: 10–21 days Mild fever + rash Rash progression: trunk → face → limbs Macules → papules → vesicles → crusts → shed without scarring Cropping = characteristic (lesions at different stages simultaneously) Complications: Pneumonia (adults; may be fatal) Fulminant encephalitis (rare) — can be part of Reye's syndrome if salicylates given Congenital Varicella Syndrome (1st trimester): skin lesions, limb hypoplasia, chorioretinitis, CNS defects Neonatal Varicella (infection near delivery): disseminated, 35% mortality If maternal rash ≥1 week before delivery: maternal IgG crosses placenta → protects baby --- Zoster (Shingles)- Reactivation of latent VZV in adults or immunocompromised patients Rash limited to a single dermatome (distribution of one dorsal root ganglion) Complications: Trigeminal nerve involvement → keratitis, conjunctivitis, iritis Cranial nerve involvement → Bell's palsy Post-herpetic neuralgia : severe pain lasting months after rash resolves; likely due to nerve damage; does not respond to antivirals --- Lab Diagnosis (VZV) Method Finding --- --- Tzanck smear Multinucleated giant cells (same as HSV) Direct Immunofluorescence Bright green intranuclear particles PCR Detects viral DNA (most specific) Serology VZV-specific antibodies via CFT, neutralisation, or ELISA --- Treatment & Prevention (VZV)- DOC: Acyclovir (inhibits DNA polymerase) Used in: immunocompromised, complicated chickenpox (pneumonia, keratitis), neonatal varicella Does not affect latency Prevention: Active: L