40. Herpesviridae. The causative agent of herpes simplex type 1 and type 2, the causative agent of varicella and herpes zoster. Human Cytomegalovirus. The causative agent of infectious mononucleosis. Other herpesviruses.

I. Family Herpesviridae – General Features

• Large, enveloped viruses, with double-stranded linear DNA genome.
• Icosahedral capsid, surrounded by tegument proteins and lipid envelope with glycoproteins.
• Replicate in the nucleus.
• Unique property: ability to establish latency in host cells and reactivate under stress or immunosuppression.
• Human herpesviruses: HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7, HHV-8.

II. Herpes Simplex Virus (HSV)

A. Types

• HSV-1: primarily oral, facial infections.
• HSV-2: primarily genital infections.

B. Pathogenesis

• Entry via mucosa or abraded skin → local replication.
• Infects sensory nerve endings → retrograde transport to sensory ganglia (trigeminal for HSV-1, sacral for HSV-2).
• Latent infection in ganglia → reactivated by stress, fever, UV light, immunosuppression.

C. Clinical Features

D. Diagnosis

• Tzanck smear: multinucleated giant cells, Cowdry type A inclusions.
• PCR: preferred (especially CSF for encephalitis).
• Direct fluorescent antibody, viral culture.
• Serology: IgG for past infection.

E. Treatment

• Acyclovir, valacyclovir, famciclovir (inhibit viral DNA polymerase).
• Early initiation in encephalitis critical.
• Lifelong latent infection persists.

III. Varicella Zoster Virus (VZV)

A. Overview

• Also called HHV-3
• Causes primary infection (chickenpox) and reactivation (shingles/Herpes zoster)

B. Pathogenesis

• Entry via respiratory droplets → replication in nasopharynx and lymph nodes.
• Viremia → disseminates to skin → chickenpox (varicella).
• Virus becomes latent in dorsal root or cranial nerve ganglia.
• Reactivation → travels down nerve → dermatomal rash (zoster).

C. Clinical Features

1. Varicella (Chickenpox)

• Fever, malaise, vesicular rash: "dew drop on a rose petal" → macule → papule → vesicle → crust.
• Rash appears in crops: lesions in different stages.
• Complications: pneumonia, cerebellar ataxia, superinfection (S. aureus).

2. Herpes Zoster (Shingles)

• Reactivation in elderly or immunocompromised.
• Painful, unilateral vesicular rash in dermatomal distribution.
• May lead to post-herpetic neuralgia.
• Herpes zoster ophthalmicus if trigeminal (V1) involved → can threaten vision.

D. Diagnosis

• Tzanck smear (shared with HSV): multinucleated giant cells.
• PCR from lesion fluid = gold standard.
• Direct fluorescent antibody.

E. Treatment

• Acyclovir, valacyclovir, famciclovir (oral for zoster; IV in severe varicella).
• Pain management for post-herpetic neuralgia.

F. Prevention

• Live attenuated vaccine:
• Varicella vaccine for children (12–15 months, booster at 4–6 years)
• Zoster vaccine (recombinant, inactivated) for ≥50 yrs
• VZIG (varicella-zoster immune globulin) for post-exposure in high-risk patients (e.g., pregnant, immunocompromised)