Herpesviruses (HSV, VZV, CMV, EBV, HHV-6/7/8)

Herpesviruses (HSV, VZV, CMV, EBV, HHV-6/7/8)

Herpesviruses (HSV, VZV, CMV, EBV, HHV-6/7/8)

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Herpesviruses - The Latent Menace

  • Core Features: All are enveloped, icosahedral, dsDNA viruses that establish lifelong latent infections.
  • HSV-1/2: Oral/genital ulcers; devastating temporal lobe encephalitis. Latency in sensory ganglia.
  • VZV (HHV-3): Varicella (chickenpox) → Zoster (shingles) reactivation in a dermatome.
  • EBV (HHV-4): Infectious mononucleosis; associated with Burkitt lymphoma & nasopharyngeal carcinoma.
  • CMV (HHV-5): Retinitis/colitis in immunocompromised; "owl's eye" inclusions.
  • HHV-6/7: Roseola infantum (high fever followed by rash).
  • HHV-8: Kaposi’s sarcoma.

Cowdry Type A Inclusion Bodies

⭐ CMV is the most common congenital viral infection in the U.S., a major cause of sensorineural hearing loss and neurodevelopmental delay.

Alpha Group (HSV, VZV) - Skin & Nerve Invaders

  • Hallmarks: Fast-growing, cytolytic, and establish lifelong latency in sensory nerve ganglia (trigeminal for HSV-1, sacral for HSV-2, dorsal root for VZV).
  • HSV-1 & HSV-2:
    • Clinical:
      • HSV-1: Gingivostomatitis, keratoconjunctivitis, esophagitis.
      • HSV-2: Genital & neonatal herpes.
    • Diagnosis: PCR is gold standard. Tzanck smear shows multinucleated giant cells.
  • Varicella-Zoster (VZV):
    • Primary (Varicella): "Chickenpox" with asynchronous ("dewdrop on a rose petal") vesicular rash.
    • Reactivation (Zoster): "Shingles" in a painful, unilateral dermatomal distribution.

Tzanck smear: multinucleated giant cells in HSV infection

⭐ HSV-1 encephalitis is the most common cause of fatal sporadic encephalitis, classically causing hemorrhagic necrosis of the temporal lobes.

Beta Group (CMV, HHV-6/7) - The Slow & Stealthy

  • Cytomegalovirus (CMV/HHV-5)
    • Transmission: Saliva, urine, blood, sexual, vertical.
    • Syndromes:
      • Immunocompetent: Mononucleosis-like (heterophile Ab-negative).
      • Immunocompromised: Retinitis ("pizza-pie"), pneumonitis, esophagitis (linear ulcers).
      • Congenital: Blueberry muffin rash, hepatosplenomegaly, sensorineural deafness.
    • Tx: Ganciclovir, valganciclovir.
  • HHV-6 / HHV-7
    • Disease: Roseola Infantum (Exanthem Subitum).
    • Presentation: 3-5 days high fever → fever breaks → rash appears (trunk first).
    • Common cause of febrile seizures.

CMV owl's eye inclusion bodies in histology

Histology Classic: CMV is famous for its large cells with prominent basophilic intranuclear "Owl's eye" inclusion bodies.

Gamma Group (EBV, HHV-8) - Oncogenic Opportunists

  • Epstein-Barr Virus (EBV / HHV-4)

    • Causes Infectious Mononucleosis (fever, pharyngitis, lymphadenopathy); transmitted via saliva.
    • Infects B-cells via CD21 receptor.
    • Diagnosis: Monospot test (heterophile antibodies), atypical lymphocytes (Downey cells).
  • Human Herpesvirus 8 (HHV-8)

    • Causes Kaposi's Sarcoma, a vascular tumor common in AIDS patients.
    • Presents as violaceous lesions on the nose, extremities, and mucous membranes.
    • Pathogenesis involves viral-encoded homologues that promote angiogenesis.

⭐ EBV is strongly associated with Burkitt Lymphoma (especially African type, t(8;14) translocation) and nasopharyngeal carcinoma.

Atypical Lymphocytes (Downey Cells) in Mononucleosis

Diagnosis & Antivirals - Lab & Pharmacy

  • Lab Diagnosis
    • PCR: Gold standard for HSV, VZV, CMV detection.
    • Tzanck Smear: Multinucleated giant cells (HSV/VZV).
    • Biopsy: "Owl's eye" inclusions (CMV), atypical lymphocytes (EBV).
  • Antiviral Therapy
    • Acyclovir/Valacyclovir for HSV/VZV.
    • Ganciclovir/Valganciclovir for CMV.
    • Foscarnet for ganciclovir-resistant CMV.

⭐ Foscarnet directly inhibits DNA polymerase without needing viral kinase activation, making it effective against resistant HSV/CMV strains.

  • HSV is the most common cause of sporadic temporal lobe encephalitis.
  • VZV reactivation causes a painful dermatomal rash (shingles).
  • CMV in the immunocompromised shows owl's eye inclusions.
  • EBV is linked to infectious mononucleosis, Burkitt lymphoma, and nasopharyngeal carcinoma.
  • HHV-6 causes roseola infantum: high fever followed by a rash.
  • HHV-8 is the causative agent of Kaposi's sarcoma.

Practice Questions: Herpesviruses (HSV, VZV, CMV, EBV, HHV-6/7/8)

Test your understanding with these related questions

A father brings in his 7-year-old twin sons because they have a diffuse rash. They have several papules, vesicles, pustules, and crusts on their scalps, torso, and limbs. The skin lesions are pruritic. Other than that, the boys appear to be well. The father reports that several children in school have a similar rash. The family recently returned from a beach vacation but have not traveled internationally. Both boys have stable vital signs within normal limits. What is the most common complication of the infection the boys appear to have?

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Flashcards: Herpesviruses (HSV, VZV, CMV, EBV, HHV-6/7/8)

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A definitive diagnosis of infectious mononucleosis is made by serologic testing for the EBV _____ antigen

TAP TO REVEAL ANSWER

A definitive diagnosis of infectious mononucleosis is made by serologic testing for the EBV _____ antigen

viral capsid

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