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★ HERPES SIMPLEX VIRUS (HSV) ★

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1. OVERVIEW

• HSV has 2 types: HSV-1 and HSV-2
• Both show >50% antigenic homology and >50% DNA (genomic) homology

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2. HSV-1 vs HSV-2 COMPARISON

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3. STRUCTURE (Fig. 56.1)

• Genome: Linear double-stranded (ds) DNA
• Capsid: Icosahedral
• Tegument (layer between capsid and envelope)
• Envelope: Lipid bilayer with glycoprotein spikes

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4. CLASSIFICATION (Table 56.2 - Family Herpesviridae)

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5. PATHOGENESIS

A. Primary Infection

• Transmission: Via abraded skin or mucosa from any site
  • HSV-1: Oropharyngeal contact with infected saliva or direct skin contact
  • HSV-2: Sexual contact; Vertical mode (mother to fetus)

B. Site of Infection

• HSV replicates at the local site of infection and can produce lesions anywhere
• HSV-1 lesions → Above the waist (M/C: around mouth)
• HSV-2 lesions → Below the waist (M/C: genital area)

C. Spread via Nerve (Neural Spread)

Virus
  ↓ invades
Local nerve ending
  ↓
Transported by RETROGRADE AXONAL FLOW to dorsal root ganglia
  ↓
Replicates further → then undergoes LATENCY

D. Latent Infection

• HSV-1 - latent in Trigeminal ganglia
• HSV-2 - latent in Sacral ganglia

• HSV does NOT replicate in latent stage and cannot be isolated during latency

E. Recurrent Infection

• Reactivation of latent virus by various stimuli:
  • Fever
  • Axonal injury
  • Physical or emotional stress
  • Exposure to UV light
• Reactivated virus travels via axonal spread back to peripheral site → replicates in skin/mucosa → produces secondary lesion

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6. INCUBATION PERIOD

• Range: 1 to 26 days
• Median: 6-8 days

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7. CLINICAL MANIFESTATIONS

A. Oral-Facial Mucosal Lesions (Most common with HSV-1)

• M/C manifestation of HSV infection overall
• M/C affected site → Buccal mucosa
• M/C primary lesion → Gingivostomatitis & Pharyngitis
• M/C recurrent lesion → Herpes labialis (painful vesicles near lips)
• Other lesions → Ulcerative stomatitis, Tonsillitis, Vesicular lesions on eyelids

B. Genital Infection (Most common with HSV-2)

C. Cutaneous Lesions (HSV via abraded skin)

D. Eczema Herpeticum

• Caused by HSV-1 in patients with chronic eczema
• Similar lesions can be produced by: Vaccinia virus or Coxsackievirus A16
• All together called → Kaposi's Varicelliform Eruption

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8. LAB DIAGNOSIS

① Specimen Collection

• Scrapings from the base of skin lesion

② Cytopathology (Tzanck Preparation)

• Stain with Giemsa stain (Wright's Stain)
• Tzanck preparation shows:
  1. Cowdry type A intranuclear inclusion body = Lipschütz body
  2. Multinucleated giant cells with faceted nuclei and ground-glass chromatin = Tzanck cells
  3. Ballooning of infected cells
  4. Margination of chromatin

③ Virus Isolation

• Most definitive tool for diagnosis of HSV
• MRC-5 cell line → preferred for isolation of HSV

④ Viral Antigen Detection

• Neutralization test
• Immunofluorescence staining with specific antisera
• Direct IF → can differentiate HSV-1 from HSV-2

⑤ HSV DNA Detection

• PCR → differentiates between HSV-1 and HSV-2
• Real-time PCR (targeting gene: glycoprotein B & UL30)
• BioFire Film Array (Automated nested multiplex PCR)

⑥ Antibody (Ab) Detection

• Ab appears → 4-7 days after infection
• Peak → 2-4 weeks
• IgM appears first → replaced by IgG
• Tests: ELISA, Indirect IF, Western blot (more accurate)
• Can differentiate HSV-1 from HSV-2 using different lines

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9. TREATMENT

• HSV-2
• Immunocompromised patients

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QUICK MEMORY AIDS 🧠

• HSV-1 = Above waist | Kids | Trigeminal | Less virulent
• HSV-2 = Below waist | Adults | Sacral | More virulent
• Tzanck prep = Cowdry A bodies (Lipschütz) + Tzanck cells (multinucleated giant cells)
• Acyclovir = Drug of choice for most HSV; Foscarnet for resistant cases
• Herpes gladiatorum = Wrestlers | Whitlow = Healthcare workers' fingers
• Kaposi's varicelliform eruption = Eczema herpeticum + Vaccinia + Coxsackie A16