Structure and Immune Evasion
The viral genome contains instructions for synthesizing about 80 proteins. Surface glycoproteins play a critical role in host cell attachment (gB, gC, gD, gH, gL) and membrane fusion (gB). Glycoproteins gB and gD serve as common antigens for both virus types.
HSV possesses potent immune evasion mechanisms:
- Glycoprotein gC binds the C3 complement component.
- The gE/gI complex captures the Fc region of IgG antibodies.
As a result of these reactions, the virus and the infected cell are shielded from immune system attacks. In the external environment, the pathogen is fragile: it is rapidly destroyed by sunlight, UV rays, detergents, and fat solvents, although it can survive for up to one month at 4 °C.
Pathogenesis and Mechanisms of Latency
The infectious process occurs in two forms: lytic (cell destruction) and latent. At the site of entry, the virus replicates in epithelial cells, causing their death and degeneration with vesicle formation. At the base of the vesicles, giant multinucleated Tzanck cells form, and specific eosinophilic intranuclear inclusions—Cowdry bodies—appear.
The virus then reaches sensory nerve endings. Nucleocapsids undergo retrograde transport along the axon to the neuronal cell body. A lifelong latent infection is established there (occurring in 70–90% of humans):
- About 1% of neurons in the ganglion are affected.
- Viral DNA does not integrate into chromosomes; instead, it exists as free circular episomes (approximately 20 copies per cell).
- HSV-1 remains dormant primarily in the trigeminal ganglia of the trigeminal nerve.
- HSV-2 hides primarily in the sacral ganglia.
Stress, hypothermia, fever, UV irradiation, or immunosuppression triggers reactivation. Viral DNA is transported back down the axon to the epithelium, causing localized inflammation.
Clinical Forms and Types of HSV
The incubation period ranges from 2 to 12 days. The evolution of the rash progresses from pruritus and edema to vesicles that rupture, form ulcers, crust over, and heal without scarring (accompanied by burning pain).
- HSV-1 (labial strain): Transmission occurs primarily in childhood via contact. It affects the upper half of the body (lips, oral mucosa, pharynx, eyes) and can cause severe encephalitis.
- HSV-2 (genital strain): Infection is associated with the onset of sexual activity. It causes ulcerating vesicles on the genitalia (in men: glans and shaft of the penis; in women: vagina, cervix). A potential association with cervical cancer has been noted.
Neonatal herpes represents a severe threat. It is transmitted intranatally (during passage through the birth canal of an HSV-2 infected mother). Manifesting on the 6th day of life, it leads to viral dissemination into internal organs and generalized sepsis. Cesarean section is indicated for prevention.
Immunity and Diagnostics
Cell-mediated immunity plays a leading role in defense (development of delayed-type hypersensitivity, NK cell activity, CD4+ and CD8+ lymphocytes). Virus-neutralizing antibodies limit intercellular spread of the pathogen but cannot prevent latent carriage and recurrences.
Diagnostic specimens include vesicle fluid, saliva, cerebrospinal fluid, and corneal scrapings. Main methods:
- Rapid diagnostics: Romanowsky-Giemsa staining of smears (identification of Tzanck cells and Cowdry bodies).
- Molecular method: PCR to identify viral DNA genes.
- Virological method: inoculation of cell cultures (HeLa, Hep-2, fibroblasts), where the virus induces a cytopathic effect (CPE) characterized by cell rounding within 24 hours.
- Biological assay: inoculation of suckling mice (development of encephalitis) or chicken embryos (formation of small pocks).
Treatment involves antiviral drugs (acyclovir, valacyclovir), ointments, and interferons. To prevent recurrent herpes during remission, an inactivated culture vaccine is used.