Structure and immune evasion
The viral genome contains instructions for the synthesis of approximately 80 proteins. Surface glycoproteins play a critical role, ensuring attachment to the host cell (gB, gC, gD, gH, gL) and membrane fusion (gB). Glycoproteins gB and gD are common antigens shared by both types of the virus.
HSV possesses powerful immune camouflage mechanisms:
- Glycoprotein gC binds the C3 component of complement.
- The gE/gI complex captures the Fc fragment of IgG antibodies.
As a result of these reactions, the virus and the already infected cell are shielded from immune system attacks. The pathogen is unstable in the external environment: it is rapidly destroyed by sunlight and UV rays, detergents, and fat solvents, although it can survive for up to one month at 4 °C.
Pathogenesis and latency mechanisms
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. Giant multinucleated Tzanck cells form at the base of the vesicles, and specific eosinophilic inclusions—Cowdry bodies—appear in the nuclei.
The virus then reaches sensory nerve endings. Nucleocapsids undergo retrograde axonal transport to the neuronal cell body. A lifelong latent infection is established there (found in 70–90% of people):
- About 1% of neurons in the ganglion are affected.
- Viral DNA does not integrate into chromosomes, existing instead as free circular episomes (approximately 20 copies per cell).
- HSV-1 hides predominantly in the trigeminal ganglia of the trigeminal nerve.
- HSV-2 hides in the sacral ganglia.
Reactivation occurs in response to stress, hypothermia, fever, UV irradiation, or immunosuppression. Viral DNA is transported back via the axon to the epithelium, causing local inflammation.
Clinical forms and HSV types
The incubation period is 2–12 days. The evolution of the rash progresses from itching and edema to the appearance of vesicles, which rupture to form ulcers, become crusted, and heal without scarring (accompanied by burning pain).
- HSV-1 (labial strain): Transmission occurs predominantly in childhood via contact. It affects the upper half of the body (lips, oral mucosa, pharynx, eyes). It is capable of causing 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 body of the penis; in women—vagina, cervix). A potential association with cervical cancer is noted.
Neonatal herpes is of particular danger. It is transmitted intranatally (during passage through the birth canal of an HSV-2-infected mother). It manifests on the 6th day of life and leads to dissemination of the virus to internal organs with the development of generalized sepsis. Cesarean section is indicated for prevention.
Immunity and diagnostics
Cellular immunity plays a leading role in protection (development of delayed-type hypersensitivity, NK cell activity, CD4+ and CD8+ lymphocytes). Neutralizing antibodies limit intercellular spread of the pathogen, but cannot prevent latent carriage and relapses.
Material for examination includes vesicle contents, saliva, cerebrospinal fluid, and corneal scrapings. Main methods:
- Express diagnostics: May-Grunwald-Giemsa or Wright-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) in the form of cell rounding within 24 hours.
- Biological assay: inoculation of suckling mice (development of encephalitis) or chicken embryos (formation of small plaques).
Treatment involves chemotherapeutic agents (acyclovir, valacyclovir), ointments, and interferons. An inactivated culture vaccine is used during remission to prevent recurrent herpes.
Briefly: answers to topical questions
What is the mechanism of action of acyclovir in the treatment of herpetic infection?
The mechanism of action of acyclovir involves sequential bioactivation of the drug inside the infected cell and blockade of viral replication.
- Penetration and initial activation — viral thymidine kinase converts the drug into acyclovir monophosphate.
- Phosphorylation cascade — host cell kinases convert the metabolite into its active form (acyclovir triphosphate).
- Competitive inhibition — the active form enters the nucleus, where it acts as a structural analogue of deoxyguanosine and competes for incorporation into viral DNA.
- Termination — upon incorporation of the drug, the addition of the next nucleotide is impossible, leading to chain termination and cessation of viral DNA synthesis.
What antiviral drugs are used to treat HSV, besides acyclovir and valacyclovir?
Besides acyclovir and valacyclovir, other systemic and local chemotherapeutic agents are used for etiotropic therapy of infections caused by Herpes simplex virus.
- Famciclovir — used orally as an alternative drug.
- Foscarnet sodium — prescribed intravenously in case of resistance to acyclovir.
- Penciclovir — used topically for recurrent herpes simplex.
- Ganciclovir and ribavirin — used as reserve drugs for children over 10–12 years old.
- Idoxuridine and vidarabine — chemotherapeutic agents for etiotropic therapy.
Local formulations such as tebrofen and floredan ointments are also used in treatment.
What is the difference between Cowdry bodies and Negri bodies?
The main difference lies in the localization of these specific inclusions inside the affected cell and the disease in which they form.
| Characteristic | Cowdry bodies | Negri bodies |
|---|---|---|
| Localization | Intranuclear inclusions | Cytoplasmic inclusions |
| Staining | Eosinophilic | Oxyphilic |
| Associated infections | Herpes simplex virus (type A), acute poliomyelitis (type B) | Rabies virus |
To remember the tropism: HSV-1 affects what is "above the waist" (face, mouth, trigeminal nerve), and HSV-2 affects what is "below the waist" (genitalia, sacral ganglia).
Class and exam questions
Why is herpes impossible to cure completely?
The virus transitions into a latent form in sensitive nerve ganglia. Its DNA persists in neuronal nuclei as free circular episomes (about 20 copies per cell), which are inaccessible to antibodies and unaffected by chemotherapeutic drugs.
What are Tzanck cells and Cowdry bodies?
Tzanck cells are giant multinucleated epithelial cells that form at the base of herpetic vesicles. Cowdry bodies are specific eosinophilic inclusions inside the nuclei of affected cells. Both signs are detected by Giemsa staining of smears.
What is the danger of herpes simplex virus for newborns?
During intranatal transmission (most commonly HSV-2), the virus disseminates to the child's internal organs. This leads to the development of generalized sepsis, which manifests on the 6th day after birth.
What else to study on this topic
- Mechanisms of delayed-type hypersensitivity (DTH) development in herpes
- Features of the CPE of herpes simplex virus in HeLa and Hep-2 cell cultures
- Experimental modeling of herpetic infection in rabbits
- Serodiagnosis of HSV: application of immunoblotting for the detection of type-specific antibodies
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