Terminology and Classification of Herpesviruses
A distinction should be made between the concepts of herpesvirus infection and herpetic infection. Herpesvirus infection encompasses all viruses of the Herpesviridae family (over 100 species), whereas 8 types are pathogenic to humans.
- HSV-1 — herpes simplex virus type 1 (fever blister virus); affects the lips, oral cavity, and facial skin.
- HSV-2 — genital herpes virus; affects the mucous membranes of the genitals.
- Type 3 — Varicella zoster, the causative agent of chickenpox and shingles.
- Type 4 — Epstein-Barr virus, the causative agent of infectious mononucleosis.
- Type 5 — cytomegalovirus (CMV).
- Type 6 — roseola infantum, mononucleosis-like syndrome.
- Type 7 — associated with chronic fatigue syndrome.
- Type 8 — associated with Kaposi sarcoma.
Based on biological properties, three subfamilies are distinguished. Alphaherpesviruses (types 1–3) persist in nerve ganglia. Betaherpesviruses (CMV, types 6 and 7) cause cytomegaly and immunosuppression. Gammaherpesviruses (types 4 and 8) exhibit tropism for T- and B-lymphocytes and can provoke lymphoproliferative disorders.
Epidemiology of HSV-1 and HSV-2
The source of infection is a sick person or virus carrier. The transmission mechanism is predominantly contact; for HSV-1, an airborne droplet pathway is also possible. Transmission vectors include saliva and the contents of herpetic vesicles. HSV-2 is transmitted sexually and transplacentally.
Universal prevalence: viral antigen is detected in 80–90% of the population, and antibodies in nearly 100%. Primary HSV-1 infection occurs in childhood (from 6 months to 3 years of age) and manifests as vesicular stomatitis. Antibodies to HSV-2 are detected after puberty, and their titer correlates with sexual activity.
Pathogenesis and Immune Evasion
Pathogenesis includes two main stages.
- Adsorption and replication of the virus at the site of entry, followed by lymphogenic and hematogenous dissemination.
- Neurogenic penetration into regional nerve ganglia, where the virus persists lifelong in a latent state. Spread along nerve fibers takes about 3 hours.
The localization of the ganglion depends on the site of entry. HSV-1 most commonly persists in the trigeminal nerve ganglia, in ophthalmic herpes — in the optic ganglion, and in nasopharyngeal lesions — in the olfactory ganglion. HSV-2 persists in the lumbosacral ganglia; its dissemination is predominantly hematogenous, which explains the possibility of developing genital herpes in adults who are not sexually active.
The immune system is unable to completely eliminate the virus: in the ganglia, it is inaccessible to humoral and cellular immunity, spreads via intercellular bridges, and induces cell fusion, avoiding contact with antibodies. Relapses are triggered by a decrease in local immunity: trauma, surgical interventions, corticosteroids, cosmetic procedures (liquid nitrogen, hyaluronic acid), stress, and sleep deprivation.
Clinical Forms
The clinical picture of HSV-1 and HSV-2 is indistinguishable, which is of no principal significance since the treatment is the same. Localized forms (orofacial herpes, stomatitis, ophthalmic herpes, genital herpes, meningitis, encephalitis) and generalized forms are conventionally distinguished; by the nature of manifestation — primary and recurrent.
- Labial herpes: prodromal burning and itching, edema and hyperemia, appearance of vesicles with clear contents, clouding, rupture, erosion, crusting.
- Herpetic fever (tracheobronchitis): acute onset, chills, dry cough, mild catarrhal symptoms; clinically indistinguishable from parainfluenza or adenovirus infection.
- Ophthalmic herpes: one of the leading causes of corneal blindness.
- CNS involvement: herpetic infection accounts for about 20% of viral encephalitides, with HSV-1 being involved in 95% of cases of herpetic meningoencephalitis.
Herpetic encephalitis begins acutely with high fever resistant to antipyretics and persistent headaches. Vesicular rash is usually absent. After 2–3 days without treatment, meningeal syndrome, seizures, general cerebral and focal symptoms, cranial nerve palsies, hemiparesis, paralysis, and possible coma develop. Involvement of the temporal lobe is characteristic, affecting personality and cognitive functions.
Diagnostics
Diagnosis of skin and mucosal lesions is based on clinical data: typical vesicular rash and association with triggering factors (stress, hypothermia, sleep deprivation).
- Serodiagnosis: HA/HI, ELISA — detection of a rising titer of class M immunoglobulins.
- Virological study: isolation of the virus from biological material.
- In CNS involvement — examination of cerebrospinal fluid: PCR diagnostics, detection of specific antigen by direct immunofluorescence.
- Brain MRI: characteristic lesions in the temporal lobes.
Treatment and Prevention
Therapy is prescribed taking into account the clinical form and severity of the disease. Etiotropic treatment includes antiviral drugs: acyclovir, valacyclovir, penciclovir, famciclovir, as well as human recombinant interferon alfa-2b. The drugs are available in the form of tablets, injection solutions, creams, and suppositories.
Pathogenetic therapy includes detoxification measures (volume depends on severity), metabolic and antioxidant support, and parenteral administration of vitamins. Specific doses and regimens are regulated by clinical guidelines.
Specific vaccination exists, however, it is used only in stable remission and monotonic relapse patterns.
Key points
- The Herpesviridae family includes 8 human-pathogenic types divided into alpha-, beta-, and gamma-subfamilies.
- HSV-1 more frequently causes orofacial lesions, and HSV-2 causes genital lesions; clinically they are indistinguishable.
- Antibodies to HSV are detected in nearly 100% of the population; primary HSV-1 infection occurs in early childhood.
- A key feature of pathogenesis is lifelong latent persistence in nerve ganglia with neurogenic spread within 3 hours.
- Immune evasion is ensured by localization in ganglia, intercellular transmission, and cell fusion.
- Herpetic meningoencephalitis is caused by HSV-1 in 95% of cases; temporal lobe involvement is characteristic.
- Diagnosis is based on clinical presentation, serology (ELISA, HA/HI), CSF PCR, and MRI.
- Etiotropic therapy — acyclovir and its analogs; vaccination is indicated during stable remission.