Human herpesvirus 8 (Kaposi sarcoma virus)

Human herpesvirus 8 (Kaposi sarcoma virus)

Human herpesvirus 8 (Kaposi sarcoma virus)

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HHV-8 Virology - The Purple Cancer Virus

  • Family: Herpesviridae (Gammaherpesvirinae subfamily).
  • Structure: Enveloped, icosahedral capsid with a linear double-stranded DNA (dsDNA) genome.
  • Cell Tropism: Primarily targets B lymphocytes and vascular endothelial cells.
  • Latency: Establishes lifelong latency, primarily in B cells. The Latency-Associated Nuclear Antigen (LANA) tethers the viral episome to host chromosomes, ensuring its persistence during cell division.

⭐ HHV-8 encodes viral homologs of host regulatory proteins (e.g., v-cyclin, v-BCL-2, v-IL-6) that promote uncontrolled cell proliferation and angiogenesis while evading apoptosis.

HHV-8 Virion Structure with Glycoproteins and ORFs

Pathogenesis - Angiogenic Hijacker

  • Primary Targets: Infects B-lymphocytes, but pathogenesis is driven by infection of vascular & lymphatic endothelial cells.
  • Molecular Piracy: Establishes latency & expresses viral proteins that mimic host molecules to drive cell growth & survival:
    • v-Cyclin: Pushes cell cycle forward (G1→S).
    • v-IL-6: Pro-inflammatory & pro-growth cytokine.
    • v-BCL-2: Anti-apoptotic.
  • Angiogenesis: Secretes viral Growth Factors (vGF) that are homologs of VEGF, directly stimulating neovascularization.

vGPCR: A viral G-protein coupled receptor is constitutively active, a key driver of VEGF secretion & proliferation.

Kaposi Sarcoma - The Classic Lesion

Kaposi sarcoma skin lesions: diverse presentations

  • Progression: Begins as flat, painless patches → evolves into raised plaques & nodules.
  • Appearance: Violaceous, purple, brown, or black lesions.
    • Often elliptical and may align with skin tension lines.
  • Common Sites:
    • Lower extremities (classic type).
    • Face, oral cavity (hard palate), genitalia (AIDS-related).
  • Histopathology:
    • Spindle cell proliferation (endothelial origin).
    • Neovascularization & slit-like vascular spaces with extravasated RBCs.

High-Yield: Lesions are often multifocal and can arise in different places simultaneously, rather than metastasizing in the traditional sense.

Associated Malignancies - Beyond the Skin

  • Primary Effusion Lymphoma (PEL)

    • Rare, aggressive B-cell lymphoma lining body cavities.
    • Presents as malignant effusions (pleural, peritoneal, pericardial) without a solid tumor mass.
    • Strongly associated with immunosuppression (e.g., AIDS).
    • Often co-infected with Epstein-Barr Virus (EBV).
  • Multicentric Castleman Disease (MCD)

    • A systemic lymphoproliferative disorder.
    • Driven by viral cytokine dysregulation, particularly viral IL-6 (vIL-6).
    • Symptoms: fever, weight loss, lymphadenopathy, splenomegaly.

High-Yield: Primary Effusion Lymphoma cells are typically CD45-positive, but negative for conventional B-cell markers like CD19 and CD20.

Primary effusion lymphoma cytology and immunohistochemistry

Diagnosis & Management - Detect & Defeat

  • Diagnosis (Gold Standard):

    • Punch biopsy of a lesion.
    • Histology: Proliferating spindle cells, neovascularization, and red blood cell extravasation.
    • PCR for HHV-8 DNA in tissue confirms diagnosis.
  • Management Strategy:

    • Treatment is tailored to the clinical subtype.

⭐ In AIDS-related KS, initiating HAART is the most crucial management step. Lesion regression often occurs as the CD4 count rises, sometimes without needing chemotherapy.

Kaposi Sarcoma Histopathology with HHV-8 IHC

High‑Yield Points - ⚡ Biggest Takeaways

  • HHV-8 is strongly associated with Kaposi sarcoma, a vascular tumor common in AIDS patients.
  • Transmission occurs primarily through saliva and sexual contact.
  • The virus infects endothelial cells, inducing angiogenesis and proliferation of spindle cells.
  • Presents as painless, purplish nodules or plaques on the skin, oral mucosa, and viscera.
  • Also linked to primary effusion lymphoma and multicentric Castleman disease.
  • Diagnosis is confirmed by biopsy showing spindle cells and neovascularization.

Practice Questions: Human herpesvirus 8 (Kaposi sarcoma virus)

Test your understanding with these related questions

A 76-year-old woman is brought to the physician because of lesions on her left arm. She first noticed them 3 months ago and they have grown larger since that time. She has not had any pain or pruritus in the area. She has a history of invasive ductal carcinoma of the left breast, which was treated with mastectomy and radiation therapy 27 years ago. Since that time, she has had lymphedema of the left arm. Physical examination shows extensive edema of the left arm. There are four coalescing, firm, purple-blue nodules on the left lateral axillary region and swelling of the surrounding skin. Which of the following is the most likely diagnosis?

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Flashcards: Human herpesvirus 8 (Kaposi sarcoma virus)

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Where is EBV latent?_____

TAP TO REVEAL ANSWER

Where is EBV latent?_____

B cells

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