Classification of Herpesviruses
The family Herpesviridae is divided into three subfamilies (Alpha-, Beta-, and Gammaherpesvirinae). Taxonomy is based on genome structure, tissue tropism, cytopathology, and the site of latency.
There are 8 human pathogenic types:
- HHV-1 (HSV-1): Herpes simplex virus type 1.
- HHV-2 (HSV-2): Herpes simplex virus type 2.
- HHV-3 (VZV): Varicella-zoster virus.
- HHV-4 (EBV): Epstein-Barr virus.
- HHV-5 (CMV): Cytomegalovirus.
- HHV-6: Roseolovirus (human herpesvirus 6).
- HHV-7: Human herpesvirus 7.
- HHV-8: Kaposi sarcoma-associated herpesvirus (KSHV).
Biological Properties of Subfamilies
For clinical convenience, viruses are grouped by subfamily, considering the target cell types, replication rate, and site of persistence.
- Alphaherpesvirinae (e.g., HSV, VZV):
- Target: Epithelial cells (cause destruction via a cytolytic effect).
- Latency: Neurons.
- Betaherpesvirinae (e.g., CMV, HHV-6, HHV-7):
- Growth rate: Slow.
- Cytopathic effect: Cytomegaly and lymphoproliferation.
- Localization (including latency): Salivary gland epithelium, kidneys, lymphocytes.
- Gammaherpesvirinae (e.g., EBV):
- Target: B lymphocytes.
- Cytopathic effect: Stimulate cell proliferation (lymphoproliferative effect).
- Localization: Lymphoid tissue, oropharyngeal epithelium, and salivary glands.
Virion Structure
Herpesviruses are oval-shaped and large (150–200 nm in diameter). Structure (from center to periphery):
- Genome: Double-stranded linear DNA consisting of short and long unique segments. Inverted repeats allow for genomic isomerization (4 isomers in HSV and CMV, 2 isomers in VZV).
- Capsid: Icosahedral symmetry, composed of 162 capsomeres.
- Tegument (matrix): A proteinaceous layer between the capsid and the envelope containing viral proteins and enzymes required to initiate replication.
- Envelope (supercapsid): Derived from the inner nuclear membrane of the host cell and studded with glycoprotein spikes for attachment.
Replication Cycle
The replication process is strictly sequential and involves both the nucleus and the cytoplasm.
Initial stages: Adsorption (attachment), fusion of the viral envelope with the plasma membrane, uncoating, and injection of DNA into the nucleus. Here, host RNA polymerase transcribes viral mRNA.
Protein synthesis (in the cytoplasm):
- Immediate-early (Alpha): Regulatory proteins that trigger subsequent transcription.
- Early (Beta): Enzymes required for genome replication (e.g., DNA-dependent DNA polymerase, thymidine kinase).
- Late (Gamma): Structural components (capsid proteins, glycoproteins).
Assembly and egress: Empty capsids are filled with DNA in the nucleus. During budding through the inner nuclear membrane, the nucleocapsid acquires its envelope. Virions are subsequently transported via the Golgi apparatus to the cell membrane and released via exocytosis or cell lysis.