Herpesvirus infections

Herpesvirus infections are a group of widespread anthroponotic infectious diseases caused by viruses of the Herpesviridae family, which are characterized by a chronic relapsing course and lifelong persistence of the pathogen in the body.

ICD-10 codes

• B00. Infection caused by the herpes simplex virus (herpes infection).
• B01. Chickenpox (Varicella zoster).
• B02. Shingles (Herpes zoster).
• B08.2. Exanthema abruptiosum (sixth disease).
• B25. Cytomegalovirus disease.
• B27. Infectious mononucleosis.

Epidemiology of herpesvirus infections

The source of herpes viruses are patients with acute forms of diseases (stomatitis, genital herpes, chickenpox, etc.) and healthy individuals infected with the corresponding virus, who periodically release it into the environment with saliva, nasopharyngeal secretions, and secretions of the mucous membranes of the genitals. It has been established that by the age of 18, more than 90% of city residents are infected with one or more of the seven clinically significant herpes viruses (HSV types 1 and 2, varicella-zoster virus, CMV, EBV, HHV-6 and -8). In most cases, primary and repeated infection occurs by airborne droplets, direct contact, or through household and hygiene items (shared towels, handkerchiefs, etc.). Oral, genital, orogenital, vertical, transfusion, and transplant routes of infection transmission have also been proven.

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What causes herpesvirus infections?

Herpes viruses can circulate in the body with a normal immune system without symptoms, but in people with suppressed immunity they can cause severe diseases with a fatal outcome. Herpes viruses have oncogenic activity and play an important role in the development of some types of lymphomas, cervical cancer, Kaposi's sarcoma, etc.

Herpes viruses are united in a large family Herpesviridae, which includes more than 100 representatives, of which 8 herpes viruses are pathogenic for humans - human herpes viruses ( HHV). Herpes viruses are a phylogenetically ancient family of large DNA viruses; they are divided into three subfamilies depending on the type of cells in which the infectious process occurs, the nature of virus reproduction, the structure of the genome, molecular biological and immunological features: α, β and γ.

Different types of herpes

Name	Abbreviation	Synonym	Symptoms
HSV type 1 (Herpes simplex Type 1)	HSV-1, HHV-1/HSV-1, HHV-1 (α-herpesvirus)	Blistering lichen virus	Oral-facial lesions, aphthous-ulcerative stomatitis, labial herpes, herpetic dermatitis, eczema herpetiformis, keratitis, conjunctivitis, encephalitis
HSV type 2 (Herpes simplex Type 2)	HSV-2, HHV-2/HSV-2, HHV-2 (α-herpesvirus)	Genital herpes virus	Genital mucosal lesions, meningitis
Varicella Zoster virus, Human herpes virus Type 3	HSV-3, HHV-3, varicella zoster virus, HZV, HHV-3 (α-herpesvirus)	Shingles virus, Herpes Zoster	Chickenpox, shingles along the sensory nerve endings, pre- and perinatal infection
EBV, human herpes virus type 4 (Epstein-Barr virus, Human herpes virus Type 4)	EBV. HHV-4 EBV, HHV-4 (γ-herpesvirus)	Infectious mononucleosis virus	Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, salivary gland lymphoepithelioma, hepatitis
CMV, human herpes virus type 5	CMV, HHV-5'CMV, HHV β-herpesvirus)	Cytomegaly virus	Pre- and perinatal infection, teratogenic effect, immunodeficiency, damage to the liver, kidneys, lungs, eyes, lymph nodes, CNS. Tendency to generalization of infection
Human herpes virus type 6	HHV-6, HHV-6 (β-herpesvirus)	Human B lymphotropic virus	Sudden exanthema of children, mononucleosis-like syndrome, chronic fatigue syndrome, encephalomyelitis, cofactor in the development of HIV infection, oral and cervical carcinomas
Human herpes virus type 7	HHV-7, HHV-7 (β-herpesvirus)		Sudden exanthema of children, chronic fatigue syndrome
Kaposi's sarcoma associated herpesvirus, Human herpes virus Type 8	HFCV, HHV-8, KSHV, HHV-8 (γ-herpesvirus)		Kaposi's sarcoma, primary disseminated lymphoma

α-Herpesviruses, including HHV-1, HHV-2, and varicella zoster virus ,are characterized by rapid viral replication and cytopathic effects on infected cell cultures. Reproduction of α-herpesviruses occurs in various cell types; the viruses can persist in a latent form, primarily in nerve ganglia.

Β-Herpesviruses are species-specific, affecting various types of cells, which increase in size (cytomegaly). They can cause immunosuppressive conditions. The infection can take a generalized or latent form; persistent infection easily occurs in cell culture. This group includes CMV, HHV-6, HHV-7.

Γ-Herpesviruses are characterized by tropism to lymphoid cells (T- and B-lymphocytes), in which they persist for a long time and can transform, causing lymphomas, sarcomas. This group includes EBV and HHV-8-herpesvirus associated with Kaposi's sarcoma.

All herpes viruses are similar in morphological features, size, type of nucleic acid (double-stranded DNA), icosadeltahedral capsid (its assembly occurs in the nucleus of the infected cell), membrane, type of reproduction, and the ability to cause chronic and latent infection in humans.

Herpes virus virions are extremely heat-labile - they are inactivated at a temperature of 50-52 °C for 30 minutes, at a temperature of 37.5 °C - for 20 hours, and are stable at a temperature of -70 °C; they tolerate lyophilization well and are preserved in tissues for a long time in a 50% glycerol solution. On metal surfaces (coins, door handles, water taps), herpes viruses survive for 2 hours, on plastic and wood - up to 3 hours, in wet medical cotton wool and gauze - during the entire time of their drying at room temperature (up to 6 hours). The unique biological properties of all human herpes viruses are tissue tropism, the ability to persist and latent in the body of an infected person. Persistence is the ability of herpes viruses to continuously or cyclically reproduce (replicate) in infected cells of tropic tissues, which creates a constant threat of developing an infectious process. Latency of herpes viruses is the lifelong preservation of viruses in a morphologically and immunochemically modified form in the nerve cells of regional (in relation to the site of herpes virus introduction) ganglia of sensory nerves. Herpes virus strains have different abilities for persistence and latency and sensitivity to antiherpetic drugs due to the peculiarities of their enzyme systems. Each herpes virus has its own rate of persistence and latency. Among those studied, HSV is the most active in this regard, EBV is the least active.

Pathogenesis of herpesvirus infections

Human infection with the above-mentioned herpes viruses is accompanied by clinical symptoms of the corresponding acute infection, on average, in no more than 50% of people, mainly in children: sudden exanthema (HHV-6), aphthous stomatitis (HSV type 1 or 2), chickenpox ( varicella zoster virus), infectious mononucleosis (EBV). mononucleosis-like syndrome (CMV). In other patients, the infection is asymptomatic, which is especially typical for adolescents and adults. In addition to the biological properties of the herpes virus strain, the course of acute and recurrent herpesvirus diseases is influenced by individual (age, gender, phylogenetic and ontogenetic) features of the immune response of an infected person to numerous antigens of the virus.

When the body's immune reactivity decreases, herpes viruses act as opportunist viruses, leading to a more severe course of the underlying disease with unusual clinical manifestations. Diseases caused by HSV, CMV, EBV are considered AIDS-indicating due to their frequent detection in this pathology.

The role of some herpes viruses (HHV-8, CMV, EBV, etc.) in the development of a number of malignant neoplasms has been proven: nasopharyngeal carcinoma, Burkitt's lymphoma, B-cell lymphoma, breast cancer, intestinal and prostate adenocarcinoma, cervical canal carcinoma, Kaposi's sarcoma, neuroblastoma, etc.

The greatest threat to health is posed by herpetic neuroinfections (mortality reaches 20%, and the incidence of disability is 50%), ophthalmic herpes (in almost half of patients it leads to the development of cataracts or glaucoma) and genital herpes.

All known herpesvirus infections can recur, but the threshold and reasons for the transformation of the acute form into a recurrent form are different for each type of herpesvirus. For example, recurrence of infections caused by HSV often occurs against the background of stress, non-specific endocrine disorders, changes in the geographical area of residence, hyperinsolation, etc. In elderly people who had chickenpox in childhood, a relapse of the infection caused by the varicella zoster virus (Varicella zoster virus) occurs in the form of herpes zoster. Subclinical relapses of CMV are most often observed in pregnant women and patients receiving immunosuppressant therapy. At the same time, infections caused by EBV recur extremely rarely and only in patients with congenital or acquired immunodeficiency.

Cloning of herpes viruses occurs according to the following scheme: spontaneous random adsorption of the original "mother" virus on the surface of the target cell, "undressing of the virion" - splitting of the membrane and capsid, infiltration of viral DNA into the nucleus of the target cell, formation and maturation of "daughter" virions by budding on the nuclear membrane. All these transformations occur under the control of enzyme systems of viral origin. In the process of maturation of "daughter" virions, their membranes, capsids and DNA are formed from amino acids, proteins, lipoproteins and nucleosides present inside the infected cell. These molecules enter the infected cell from the interstitial spaces as the intracellular reserves are depleted. The first generation of "daughter" herpes viruses begins to enter the environment (intercellular spaces, blood, lymph and other biological environments) after approximately 18 hours. Herpes viruses remain in a free state for a very short period (from 1 to 4 hours) - this is the typical duration of the period of acute intoxication in herpesvirus infections. The lifespan of each generation of formed and adsorbed herpes viruses is on average 3 days.

Symptoms of herpesvirus infections

For practical purposes, herpesvirus infections are classified taking into account the localization of the process, recurrence and etiology.

Acute and recurrent herpesvirus diseases in humans

Type of herpes virus	Primary diseases	Recurrent diseases
HSV type 1	Gingivostomatitis. keratoconjunctivitis	Oral herpes, keratoconjunctivitis, encephalitis
HSV type 2	Genital herpes, neonatal herpes, disseminated herpes	Genital herpes
Varicella zoster virus	Chicken pox	Herpes zoster, disseminated chickenpox in immunodeficiency
EBV	Infectious mononucleosis, B-cell proliferation	Infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma
CMV	Congenital anomalies, cytomegalovirus in immunodeficiency	Cytomegalovirus in patients after organ transplantation, retinitis, colitis or neuroinfection in AIDS
Human herpes virus 6	Erythema neonatorum	Systemic diseases after transplantation
Human herpes virus 7	Erythema neonatorum	Unknown
Human herpes virus 8	Kaposi's sarcoma	Unknown

Diagnosis of herpesvirus infections

Diagnosis of herpesvirus infections is based on the use of ELISA methods, immunofluorescent antibody methods, IB, PCR, and electron microscopy.

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Treatment of herpesvirus infections

Treatment of herpesvirus infections remains a complex task. A long-term chronic process leads to a negative immune restructuring of the body: the development of secondary immune deficiency, suppression of cellular immunity reactions, a decrease in the non-specific protection of the body, expressed in a decrease in the ability of leukocytes to produce a- and y-interferon, hypoimmunoglobulinemia, sensitization to viral antigens. Taking into account the etiology, pathogenesis, symptoms of herpesvirus infections, numerous drugs of etiotropic and immunocorrective action have been proposed for the treatment of herpes diseases, which are divided into three groups by the mechanism of action.