Herpesviruses Overview - The Latent Lurkers
- Large, enveloped viruses; icosahedral capsid; linear dsDNA genome.
- Unique: Proteinaceous tegument between capsid and envelope.
- Hallmark: Establish lifelong latent infections; periodic reactivation.
⭐ All herpesviruses are dsDNA, enveloped, establish latency, and are notorious for reactivation.
| Subfamily | Key Features | Latency Site(s) | Examples |
|---|---|---|---|
| Alpha (α) | Fast-growing, cytolytic | Sensory ganglia | HSV-1, HSV-2, VZV |
| Beta (β) | Slow-growing, cytomegalic | Glands, kidneys, lymphoreticular cells | CMV, HHV-6, HHV-7 |
| Gamma (γ) | Variable growth, lymphoproliferative | Lymphoid tissue | EBV, KSHV (HHV-8) |
Alphaherpesviruses (HSV, VZV) - Rapid Raiders
- Neurotropic, establish latent infections; cause vesicular lesions.
- Common Dx: Tzanck smear (multinucleated giant cells), Cowdry type A intranuclear inclusions, PCR.
| Virus | Diseases | Transmission | Latency Site |
|---|---|---|---|
| HSV-1 | Oral/ocular lesions, encephalitis, labialis | Contact, saliva | Trigeminal ganglia |
| HSV-2 | Genital/neonatal herpes | Sexual, perinatal | Sacral ganglia |
| VZV | Varicella (chickenpox), Zoster (shingles) | Respiratory, contact | DRG/cranial ganglia |
⭐ Herpes Simplex Encephalitis (HSV-1) is the most common cause of sporadic viral encephalitis, characteristically affecting temporal lobes.
Betaherpesviruses (CMV, HHV-6/7) - Slow & Stealthy
-
Cytomegalovirus (CMV)
- Targets: Monocytes, lymphocytes, epithelial cells.
- Clinical: Congenital (microcephaly, deafness); Immunocompromised (retinitis, colitis, pneumonitis); Mononucleosis-like syndrome.
- Dx: "Owl's eye" basophilic intranuclear inclusions; PCR.
- 📌 CMV: Can Make Various problems (Congenital, Compromised hosts), Cells Massively Vacuolated (Owl's eye).
-
Human Herpesvirus 6 (HHV-6) & 7 (HHV-7)
- Targets: T-lymphocytes.
- Clinical: Roseola infantum (Exanthem subitum) - high fever followed by rash.
- 📌 HHV-6: Roseola - Fever then Rash on 6th day (approx).
⭐ Cytomegalovirus (CMV) is the most common viral cause of congenital infections and a major pathogen in transplant recipients.
Gammaherpesviruses (EBV, KSHV) - Oncogenic Opportunists
Lymphotropic, establish latency, oncogenic, especially in immunosuppression.
| Feature | EBV (HHV-4) | KSHV (HHV-8) |
|---|---|---|
| Target Cells | B-cells (CD21), epithelial cells | Endothelial cells, B-cells |
| Key Diseases | Infectious Mononucleosis, Burkitt's Lymphoma, Nasopharyngeal Ca, Oral Hairy Leukoplakia | Kaposi's Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman's |
| Diagnosis | Monospot, Atypical lymphocytes (Downey), Serology | Biopsy, PCR (HHV-8 DNA), LANA-1 serology |
| 📌 KSHV: Kaposi's Sarcoma Herpes Virus - Kisses goodbye to healthy skin in AIDS. |
⭐ EBV infects B-lymphocytes via the CD21 receptor, causing infectious mononucleosis and various cancers.
Herpesvirus Dx & Rx - Herpes Busters
- Dx: PCR (CSF, lesions), Serology (IgM/IgG), Tzanck smear (multinucleated giant cells).
- Rx: Antivirals
Drug MoA (Key Enzyme) Key Indications Major Toxicities Acyclovir DNA pol (TK) HSV, VZV Nephro, Neuro Valacyclovir Acyclovir prodrug HSV, VZV Nephro, Neuro Ganciclovir DNA pol (UL97) CMV Myelosuppression Valganciclovir Ganciclovir prodrug CMV Myelosuppression Foscarnet DNA pol (direct) Res. HSV/CMV Nephro, Electrolytes ↓ Cidofovir DNA pol (nucleotide) Res. CMV Nephro (severe), Uveitis
📌 Acyclovir: A Cycle-ovir stops viral DNA cycle.
⭐ Foscarnet: pyrophosphate analog, directly inhibits DNA pol (no phosphorylation needed); for resistant strains.
High-Yield Points - ⚡ Biggest Takeaways
- All herpesviruses are dsDNA, enveloped and establish lifelong latency.
- HSV-1 (oral), HSV-2 (genital); VZV (chickenpox/shingles); Tzanck smear shows multinucleated giant cells.
- CMV is the most common congenital infection with characteristic "owl's eye" inclusions.
- EBV causes infectious mononucleosis and is linked to Burkitt's lymphoma & nasopharyngeal carcinoma.
- HHV-6 causes Roseola infantum (exanthem subitum); HHV-8 causes Kaposi's sarcoma.
- Acyclovir and its derivatives are key antivirals for HSV and VZV infections_
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